december 2-4, 2015 · our program this year will focus on human disease diagnostics, therapeutics...

DECEMBER 2-4, 2015WINTHROP ROCKEFELLER INSTITUTE

A WINTHROP ROCKEFELLER CONFERENCE

THIS WINTHROP ROCKEFELLER CONFERENCE IS A PARTNERSHIP AMONG

SPECIAL THANKS TO

THE WINTHROP ROCKEFELLER CHARITABLE TRUST

AND

THE ARKANSAS RESEARCH ALLIANCE

FOR THEIR GENEROUS SUPPORT

FUNDING FOR THIS CONFERENCE WAS MADE POSSIBLE, IN PART, BY THE FOOD AND DRUG ADMINISTRATION THROUGH GRANT 5 R13 FD 005073-02, V IEWS EXPRESSED IN WRITTEN CONFERENCE MATERIALS OR PUBLICATIONS AND BY SPEAKERS AND MODERATORS DO NOT NECESSARILY REFLECT THE OFFICIAL POLICIES OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES; NOR DOES ANY MENTION OF TRADE NAMES, COMMERCIAL PRACTICES, OR ORGANIZATION IMPLY ENDORSEMENT BY THE UNITED STATES GOVERNMENT.

3W I N T H R O P R O C K E F E L L E R I N S T I T U T E - N A N O T E C H N O L O G Y F O R H E A L T H C A R E C O N F E R E N C E

WELCOME ..................................................................................................................05

ORGANIZING COMMITTEE ..........................................................................................06

AGENDA .....................................................................................................................07

Wednesday, December 2, 2015 ........................................................................................ 07

Thursday, December 3, 2015 ........................................................................................... 08

Friday, December 4, 2015 ............................................................................................... 09

SPEAKER BIOGRAPHIES .............................................................................................10

WEDNESDAY, DECEMBER 2, 2015 ...............................................................................23

Plenary Abstracts ........................................................................................................... 25

Workshop Abstracts ....................................................................................................... 33

Poster Presentation Abstracts ........................................................................................ 43

THURSDAY, DECEMBER 3, 2015 ..................................................................................59

Plenary Abstracts ........................................................................................................... 61


FRIDAY, DECEMBER 4, 2015........................................................................................75


SCIENCE AS ART ........................................................................................................93

Judges ........................................................................................................................... 95

Entries ........................................................................................................................... 97

CONTENTS

4 N A N O T E C H N O L O G Y F O R H E A L T H C A R E C O N F E R E N C E - W I N T H R O P R O C K E F E L L E R I N S T I T U T E


On behalf of conference chair Paul Howard, Ph.D., the organizing committee and everyone here at the Winthrop Rockefeller Institute, welcome to the Sixth Nanotechnology for Health Care Conference. We are honored by your presence here atop beautiful Petit Jean Mountain.

Our program this year will focus on human disease diagnostics, therapeutics and prevention using nanotechnology, and approaches to developing international standards and methods for measuring nanomaterials and their biological impact. There will also be a special workshop focused on funding opportunities and strategies. These topics represent some of the outstanding work being done in the state of Arkansas, and we are eager to learn more about these exciting fields from our distinguished lineup of speakers.

We are also excited to welcome Sir Harold Kroto as the conference’s first Nobel Laureate keynote speaker. It is a tremendous honor to have him join us, and his presence highlights the caliber of research and discussion you will learn about and take part in during this conference. Kroto and the rest of our presenters will have plenty of knowledge and expertise to share with you.

Throughout the conference, we hope that you take advantage not only of the opportunities to learn about new research and emerging technologies, but also to connect with colleagues and develop relationships that will benefit you both personally and professionally. This conference links the best and brightest from Arkansas and the mid-South with leading scientists from around the country and the world. We hope you find your time here this week to be beneficial and invigorating.

All good wishes,

Marta Loyd, Ed.D. Executive Director Winthrop Rockefeller Institute

WELCOME


CHAIR

Paul Howard

COMMITTEE MEMBERS

Alex Biris, Ph.D. (UALR)

Michael Borrelli, Ph.D. (UAMS)

Roger Buchanan (Arkansas Research Alliance)

Thomas Flammang, Ph.D. (FDA)

Ekaterina Galanzha, Ph.D. (UAMS)

Rob Griffin, Ph.D. (UAMS)

Ralph Henry, Ph.D. (UAF)

Serguei Liachenko, Ph.D. (FDA)

Gail McClure, Ph.D. (Arkansas Science and Technology Authority)

Dmitry Nedosekin, Ph.D. (UAMS)

Anil Patri, Ph.D. (FDA)

Eric Peterson, Ph.D. (UAMS)

Haio Qu, Ph.D. (FDA)

Greg Salamo, Ph.D. (UAF)

Ashok Saxena, Ph.D. (UAF)

Holly Stehle (FDA)

Shraddha Thakkar, Ph.D. (FDA)

Vladimir Zharov, Ph.D. (UAMS)

2015 ORGANIZING COMMITTEE


AGENDA

WEDNESDAY, DECEMBER 2, 2015

9:00 – 10:00 AM Registration – Front Lobby

10:00 – 10:15 AM Meeting Opening – Show Barn Hall

10:20 – 11:15 AM Nobel Keynote: Creativité Sans Frontières – Show Barn HallSir Harold Kroto, FRS, Florida State University, U.S.

11:15 AM – 12:10 PM Conference Keynote: Bioanalytics Using Single Plasmonic Nanostructures – Show Barn HallWolfgang Fritzsche, Leibniz Institute of Photonic Technology, Jena, Germany

12:10 – 1:00 PM Lunch Buffet – Conference Dining

1:00 –1:45 PMPlenary Session 1: Polymeric Micelles - A Transformative Technology at the Clinical Stage – Show Barn HallAlexander Kabanov, University of North Carolina, U.S.

1:45 –2:30 PMPlenary Session 2: Who Cares About Uncertainties? Measurement Challenges for Nanomaterials – Show Barn Hall Jan Herrmann, National Measurement Institute, Australia

2:30 – 3:00 PM Break – Flagstone Foyer

3:00 – 6:00 PM

Workshops 1 & 2 – Petit Jean I and Petit Jean II

Strategies for Targeted Delivery of Nanoparticles and Nanosensors – Petit Jean IWolfgang Fritzsche, Leibniz Institute of Photonic Technology, Germany; Esther Chang, Georgetown University Medical Center, U.S.; Alexander Kabanov, University of North Carolina, U.S.; Jingyi Chen, University of Arkansas, U.S.

Best Practices and Standards for Nanomaterial Characterization – Petit Jean IIKate Chalfin, ASTM, U.S.; Jan Herrmann, National Measurement Institute, Australia; Frank Weichold, FDA, U.S.

6:30 – 7:30 PM Dinner – Conference Dining

7:30 – 8:30 PM Poster Presentation and Reception – Governor’s Conference Room

8:30 –10:00 PM Networking – River Rock Grill


AGENDA

THURSDAY, DECEMBER 3, 2015

7:00 – 8:00 AM Breakfast – Conference Dining

8:00 – 8:45 AMPlenary Session 3: Polymeric Nanoparticles for Oral Delivery of Drugs: Efficacy and Safety Assessment – Show Barn HallCristina Sabliov, Louisiana State University, U.S.

8:45 – 9:30 AMPlenary Session 4: Nanogenerators for Self-powered Systems and Piezsotronics for Smart Devices – Show Barn Hall Zhong Lin Wang, Georgia Tech, U.S.

9:30 – 10:00 AM Break – Flagstone Foyer

10:00 AM – 12:00 PM


Interactions, Impact and Use of Nanomaterials for Complex Biological Systems – Petit Jean ICristina Sabliov, Louisiana State University, U.S.; David Anderson, UT Knoxville, U.S.; Madhu Dhar, UT Knoxville, U.S.; Syed Ali, FDA/NCTR, U.S.

Biosensors and Transducers for Medical Applications – Petit Jean IIMorten Jensen, University of Arkansas, U.S.; Z.L. Wang, Georgia Tech, U.S.; John Shock, UAMS, U.S.

12:00 – 1:00 PM Lunch Buffet – Conference Dining

1:00 – 3:00 PM Workshop 5 – Brain and Nanotechnology: Strategies for EPSCoR and other Multi-investigator, Programmatic Research Funding Opportunities - Rock Theater

3:00 – 5:00 PM Team Building Activities – Institute Grounds

5:00 – 6:30 PM Dinner – Conference Dining

6:30 – 8:00 PM Breakout Group Discussions on Funding Opportunities and Collaborative Efforts on Brain and Nanotechnology – Show Barn Hall

8:00 – 10:00 PM Networking – River Rock Grill


AGENDA

FRIDAY, DECEMBER 4, 2015

7:30 – 8:30 AM Breakfast – Conference Dining

8:30 –11:30 AM


Arkansas Consortium on Carbon-based Nanostructures: Carbon Nanotubes, Fullerenes and Graphene – Petit Jean IRoger Buchanan, Arkansas State University, U.S.; Jacob Berlin, City of Hope, U.S.; Anil Patri, FDA/NCTR, U.S.; Ravi Barabote, University of Arkansas, U.S.; Radwan Al Faouri, University of Arkansas, U.S.; Gisela Erf, University of Arkansas, U.S.; Shawn Bourdo, UALR, U.S.; Alexei Basnakian, UAMS, U.S.; Dmitry Nedosekin, UAMS, U.S.

Workshop 7 – Nanoimaging and Nanoneuroimaging: Special Focus on Imaging Modalities That Detect Nanomaterials, Primarily MRI (?MRI + X) – Petit Jean IIBenham Badie, City of Hope, U.S.; Dmitiri Artemov, Johns Hopkins University, U.S.

11:30 AM –12:00 PM Workshop Closing – Show Barn Hall

12:00 –1:00 PM Lunch

1 0 N A N O T E C H N O L O G Y F O R H E A L T H C A R E C O N F E R E N C E - W I N T H R O P R O C K E F E L L E R I N S T I T U T E

SPEAKER BIOGRAPHIES

Sir Harold (Harry) Kroto is currently a Francis Eppes Professor of Chemistry at Florida State University, where he is carrying out research in nanoscience and cluster chemistry as well as developing exciting new Internet approaches to STEM educational outreach. In 1996 he was knighted for his contributions to chemistry and later that year was one of three recipients of the Nobel Prize for Chemistry. He is a Fellow of the Royal Society of London and holds an emeritus professorship at the University of Sussex in Brighton, United Kingdom. The research program focuses on the complex range of molecular constituents in carbon vapor; the development of novel 2- and 3-D metal-cluster/organic frameworks as well as peptides; the stabilization of small fullerenes; and carbon nanotube based devices behavior.

Kroto obtained a first class BSc honors degree in chemistry (1961) and a doctorate in molecular spectroscopy (1964) at the University of Sheffield (U.K.). After postdoctoral positions at the National Research Council in Ottawa, Canada, (1964-66) and at the Murray Hill Bell Laboratories (New Jersey, U.S.) in 1966-67 he started his independent academic career at the University of Sussex. In 1970 his research group conducted laboratory began spectroscopic studies on long linear carbon chain molecules with colleague David Walton. This research led to radio astronomy searches with Takeshi Oka and Canadian astronomers (Lorne Avery, Norman Broten and John McLeod) at the National Research Council in Canada, which made the surprising discovery that they existed in unusually copious amounts in certain regions of interstellar space. At the same time he developed flash thermolytic synthetic methods to create new metastable species and intermediates with multiple bonds between carbon and second and third row atoms (S, Se and P) and applied microwave spectroscopic techniques to detect and characterize them. The work on multiply bond carbon-phosphorus species (with Sussex colleague John Nixon) created the first molecule with a C=P double bond and the second with a C≡P triple bonded species. The general synthetic techniques developed opened up the exciting new fields of Phosphaalkene and Phospahalkyne Chemistry. Conclusions derived from the earlier radioastronomy breakthrough on carbon species in space led to experiments in 1985 together with Robert Curl, Richard Smalley and research students Jim Heath, Sean O’Brien and Yuan Liu at Rice University (Texas). These laboratory experiments, which simulated the chemical reactions in the atmospheres of red giant stars uncovered the existence of C60 Buckminsterfullerene, the third well characterized form of carbon, for which he together with Curl and Smalley received the 1996 Nobel Prize in Chemistry.

In 1995, he launched the Vega Science Trust to create science films of sufficiently high quality for broadcast on U.K. network television. He is now heavily involved with GEOSET (Global Educational Outreach for Science, Engineering, and Technology), which is a program he initiated after moving to Florida State University. (Read more at www.geoset.info and www.geoset.fsu.edu.) GEOSET seeks to exploit the revolutionary creative dynamics of the Internet (which Kroto calls it the GooYouWiki-World) to improve the general level of science understanding an awareness worldwide. Numerous universities in the U.S., U.K., Japan, Croatia and

NOBEL KEYNOTE

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Wolfgang Fritzsche, Ph.D., has been the head of the Nano Biophotonics department at the Leibniz Institute of Photonic Technology (IPHT) in Jena, Germany, since 2001. He completed his doctorate at the Max-Planck-Institute for Biophysical Chemistry in Göttingen, Germany, and then worked as a postdoc at the Iowa State University, U.S., on biological AFM and image processing before returning to Jena. His research interests are molecular plasmonics and nanotechnology with a special focus on DNA-nanoparticle complexes and their integration into chip environments for bioanalytical and nanophotonic applications. Fritzsche is the initiator and organizer of the “DNA-Nanotechnology” and the “Molecular Plasmonics” symposia in Jena.

Radwan Al Faouri, Ph.D., is a research assistant professor at the Institute for Nanoscience and Engineering at the University of Arkansas in Fayetteville, Arkansas, U.S. Al Faouri’s research currently focuses on investigating the characteristics of bi-nano materials, using electrophysiology techniques to study the behavior of nano channels, and using the patch clamp technique to investigate the functionality of ion channels in cells and giant liposomes. Prior to his time at the University of Arkansas he served as visiting professor at the University of Central Arkansas in Conway, Arkansas, U.S., as part of the Department of Physics. He is a member of the Biophysics Society and the American Physical Society. In 1999 he was awarded the King Hussein medal in chess and is the holder of a United Nations badge.

Sayed Ali, Ph.D., is the senior biomedical research scientist and head of the Neurochemistry Laboratory for the Division of Neurotoxicology at the National Center for Toxicological Research/FDA, in Jefferson, Arkansas, U.S. Ali is also an adjunct professor of biochemistry and molecular biology; neurology; and pharmacology and toxicology at the University of Arkansas for Medical Sciences, Little Rock, Arkansas, and at the department of pharmacology at Duke University

PRESENTERS

CONFERENCE KEYNOTE

Spain are now contributing to GEOSET’s rapidly growing, globally accessible and freely available cache of science educational material in modular form designed to help teachers. A most exciting aspect of this initiative has been the revelation that graduate and undergraduate students are often exceptionally good at creating educational modules.

He has numerous awards including the Copley Medal, Faraday Lectureship of the Royal Society as well as the Tilden Lectureship and Longstaff Medal of the Royal Society of Chemistry. Other awards include the Louis Vuitton – Moet Hennessy Science pour l’Art prize and the Italgas Prize for Innovation. He holds more than 40 honorary degrees from universities all over the world and is a Freeman of the City of Torino. From 2004 to 2012 he was on the Board of Scientific Governors at Scripps Institute and serves on several other academic advisory boards. He was elected a Foreign Associate of the National Academy of Sciences in 2007.


Medical Center, Durham, North Carolina, U.S. Ali’s laboratory is studying the effects of nanomaterials on the central nervous system and has demonstrated that NPs are capable of generating oxidative stress and free radicals, which may in turn produce neurotoxicity. Carbon nanotubes (CNTs) and graphenes are considered to have revolutionized the field of nanotechnology because of their light weight. However, this property can be potentially hazardous if it allows CNTs or graphene to reach the lung and blood stream after environmental exposure. Using in vitro and in vivo approaches, Ali plans to investigate the potential of engineered metallic NPs and CNTs to produce adverse effects on cellular systems due to their ability to cross the blood-brain barrier (BBB).

David E. Anderson, DVM, MS, DACVS, is the head of the department of large animal clinical sciences at the University of Tennessee Institute of Agriculture, Knoxville, Tennessee, U.S. His research goal is to advance clinical medicine through the development of new methodology for the study of disease and new technology for repair or regeneration of injured or diseased tissues. To that end, his expertise has been focused on development of animal models for in vivo research. In his animal modeling research, Anderson has worked with or developed a number of methods for achieving research goals. He has developed animal models for nutrition, orthopedics and pancreatic cancer, among others. He has also worked on bovine-focused minimally invasive surgery models and developed training models for calf castration and bovine dehorning.

Dmitri Artemov, Ph.D., graduated from Moscow State University with a major in physics and continued his education at the Russian Academy of Sciences where he got his doctorate in physics and mathematics for MRI in solids. He continued pursuing his goals in biomedical applications of magnetic resonance by completing postdoctoral training at the laboratories of Dr. Haase at the University of Wuerzburg and Dr. Glickson at Johns Hopkins University. He currently is an associate professor of radiology and oncology at the Johns Hopkins University School of Medicine. In 2009, Artemov was elected a fellow of the International Society for Magnetic Resonance in Medicine. His major scientific interests are developing novel molecular targeting methods for highly sensitive and specific molecular imaging and therapy of cancer, including targeting receptors expressed in the cancer vasculature. This approach is not limited by delivery barriers and can help to develop effective targeting strategies against tumors with no known molecular targets, such as triple-negative breast cancer.

Behnam Badie, M.D., is an expert in the field of surgical neuro-oncology. He currently serves as vice chair of the department of surgery, chief of the division of neurosurgery and is also the director of the Brain Tumor Program at the City of Hope National Medical Center. Prior to joining the department of neurosurgery, Badie was an associate professor and vice chair of the department of neurological surgery at the University of Wisconsin in Madison where he also served as the director of the Comprehensive Brain Tumor Program. He was also vice chair of academic affairs at the University of Wisconsin Medical School where he was honored as the best teacher in 2002. He earned his Bachelor of Science in biochemistry, magna cum


laude, and his medical degree from the University of California, Los Angeles (UCLA). He completed a seven-year residency in neurosurgery at UCLA. Badie has published more than 145 articles, book chapters and abstracts in peer-reviewed journals including Cancer Research, Clinical Cancer Research, Nanomedicine, Glia, Journal of Neurosurgery, Journal of Neuroimmunology and Journal of Neuroradiology. He is an active member of the American Association of Neurological Surgeons, Congress of Neurological Surgeons, Society of Neuro-oncology and others. Badie has also been named on both the “Top Doctors of America” and “Americas Top Doctors for Cancer” since 2002. Badie has clinical interests in the treatment of skull base tumors, acoustic neuromas, pituitary tumors, meningiomas and other nervous system tumors. His research focuses on brain tumor immunology. More specifically, his research team is attempting to develop novel immunotherapy approaches for malignant brain tumors through the activation of microglia and macrophages using nanoparticles. His research is currently funded by the NCI and various public and private foundations.

Ravi Barabote, Ph.D., is an assistant professor with the department of biological sciences at the University of Arkansas, Fayetteville, Arkansas, U.S. He is currently a member of the American Society for Microbiology, MidSouth Computational Biology and Bioinformatics Society, and the South Central Branch of the American Society for Microbiology. In 2014 he served as the conference chair at the annual meeting of the South Central Branch of the American Society for Microbiology. Barabote has also served on the scientific advisory board NIH-funded Transporter Classification Database and was the recipient of the Innovative Development Award (2009) from the Committee on Research at the University of California. He has more than 30 publications and two patents.

Jacob Berlin, Ph.D., joined the department of molecular medicine at the Beckman Research Institute of City of Hope (Duarte, California, U.S.) in 2010 as an assistant professor. Berlin’s laboratory has quickly gained recognition for their work on using nanoparticles to detect and treat cancer. In the past year, they have published in leading journals for the fields of material science (Advanced Materials) and nanotechnology (ACS Nano). Their work has been featured on the covers of Advanced Healthcare Materials and the Journal of Materials Chemistry B. In 2014, Berlin was selected as one of the “Rising Stars and Young Nanoarchitects in Materials Science” by the Royal Society of Chemistry. Berlin was also awarded the STOP CANCER Research Career Development Award in 2012. Berlin lab’s research is currently supported by the National Cancer Institute (R01), National Institute of Neurological Disorders and Stroke (R21), The Rosalinde and Arthur Gilbert Foundation and the Anthony F. & Susan M. Markel Fund of The Community Foundation Serving Richmond and Central Virginia. Previous funding sources include Mary Kay, STOP CANCER, The Kenneth T. and Eileen L. Norris Foundation, ThinkCure!, UC Riverside-City of Hope collaborative grant and Caltech-City of Hope Biomedical Initiative. Prior to joining City of Hope in 2010, Berlin received his bachelor’s degree, magna cum laude, in chemistry from Harvard University (Boston, Massachusetts, U.S.) and his doctorate from the California Institute of Technology (Pasadena, California, U.S.). He undertook


postdoctoral study from 2006–2010 at Massachusetts Institute of Technology (Boston, Massachusetts, U.S.) and Rice University (Houston, Texas, U.S.).

Shawn Bourdo, Ph.D., has held an appointment as a research associate in the Center for Integrative Nanotechnology Sciences (CINS) since 2009, after receiving his doctorate from the department of applied science at the University of Arkansas at Little Rock (UALR). He obtained his bachelor’s and master’s degrees from the department of chemistry at UALR, where he began his research endeavors investigating inherently conducting polymers (ICPs). He studied the chemistry and electronic material properties of Carbon-ICP composites during his doctoral studies, which furthered his interest in the multitude of optoelectronic applications of both carbon nanomaterials and ICPs. His expertise lies in the synthesis, processing and characterization of polymers and composite materials. Since his appointment at CINS, he has overseen projects on photovoltaics and graphene toxicity, and he continues to explore processing techniques and applications for carbon nanomaterials and ICPs.

Roger Buchanan, Ph.D., completed his doctorate in cell biology at the University of Delaware in 1990, was a postdoctoral fellow at the National Institutes of Health (Bethesda, Maryland, U.S, and Woods Hole, Maryland, U.S.) before coming to Arkansas as an assistant professor of biology at Arkansas State University in 1992. While at ASU, he directed several large research and educational programs funded by the National Science Foundation, the National Institutes of Health and the U.S. Department of Defense. He also held several administrative positions there, including department chair, director of the Environmental Sciences and Molecular BioSciences Ph.D. programs and the Judd Hill Chair of Biotechnology before retiring in August 2012. He joined the Arkansas Research Alliance in October 2012 and is the scientific coordinator of the Arkansas Research Consortium in Nanotechnology. This consortium is a cooperative effort that currently involves more than 30 researchers at three Arkansas universities (University of Arkansas, University of Arkansas at Little Rock and University of Arkansas for Medical Sciences) and the National Center of Toxicological Research. The consortium has received funding from the U.S. Food and Drug Administration and the state of Arkansas. Its current research is focused on understanding the toxicology of graphene-based nanomaterials.

Kate Chalfin is a manager of technical committee operations at ASTM International, a globally recognized leader in the development of voluntary consensus standards, based out of Conshohocken, Pennsylvania, U.S. She has seven years of experience in standards development and has been with ASTM for nine years. Chalfin manages seven ASTM technical committees, including E56 on Nanotechnology, E07 on Nondestructive Testing, and E50 on Environmental Assessment, Risk Management, and Corrective Action. As part of her role, she acts as the liaison between technical committee members and various government entities, trade associations and other standard developing organizations, and works to improve services to the society’s members. Chalfin


received her Bachelor of Science in accounting from La Salle University and her Master of Business Administration from Saint Joseph’s University, both in Philadelphia, Pennsylvania, U.S.

Esther H. Chang is a member of the departments of oncology and otolaryngology at the Lombardi Comprehensive Cancer Center of Georgetown University Medical Center. Before joining Georgetown University, Chang held positions in the National Cancer Institute as a cancer expert, as a professor in the department of surgery at Stanford University and as a professor in the department of pathology at the Uniformed Services University of the Health Sciences. Currently, she is serving as the president of the American Society for Nanomedicine and she is also an executive board member of the International Society for Nanomedicine in Basel. Chang is the founding scientist of and a senior consultant for SynerGene Therapeutics, Inc. Chang’s research efforts have focused primarily on the molecular mechanisms of carcinogenesis and in translating this basic information into new clinical modalities. Delineation of the roles of various genetic factors, both oncogenes and tumor suppressor genes, in the multistep process of tumor formation is the key to improved diagnosis and effective therapy of cancer. She was the first to identify human versions of a mouse viral oncogene and to demonstrate the role of these “ras oncogenes” in carcinogenesis. Chang has more than 140 publications, is the inventor of 115 issued patents, and has served as a member of a number of scientific advisory boards for the National Cancer Institute, NASA, the U.S. Military Cancer Institute and the Department of Energy. She also has dedicated much time to the education of undergraduate, graduate and medical students. Chang has held peer-reviewed grants from the NIH for more than 29 years without interruption.

Jingyi Chen, Ph.D., received a Bachelor of Science in chemistry from Sun Yat-Sen University, China (1997). She came to the United States in 2001, received a Master of Arts in chemistry (with professor Kimberly A. Bagley) from SUNY College at Buffalo (2002) and a doctorate in analytical chemistry (with professor Younan Xia) from the University of Washington at Seattle (2006). She worked as a postdoctoral researcher with professor Stanislaus S. Wong at Brookhaven National Laboratory and then as a research assistant professor of biomedical engineering at Washington University in St. Louis. In 2010, she started as an assistant professor of chemistry and biochemistry at the University of Arkansas, Fayetteville, Arkansas, U.S. Her research interests include synthesis, characterization and surface modification of nanostructured functional nanomaterials for energy conversion, tribology and biomedical applications.

Madhu Dhar, Ph.D., received her doctorate in chemistry with a specialization in biochemistry/molecular and cellular biology. She is currently appointed as an associate professor in the department of large animal clinical sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, U.S. She is the director of the Large Animal Regenerative Medicine program at UT. Madhu Dhar started the molecular and cellular research in this clinical department in 2009 and, since then, her laboratory focuses on basic and clinical research involving cell-based


therapies. She currently mentors three doctorate students with interest in animal models of bone, cartilage and neural regeneration.

Gregory K. Farber, Ph.D., has a Bachelor of Science from Penn State University in chemistry (1984) and a doctorate from MIT in physical chemistry (1988). Farber’s research in graduate school involved determining the three-dimensional structure and mechanism of the enzyme xylose isomerase in the laboratory of Dr. Gregory A. Petsko. After graduate school, Farber received a Life Sciences Research Fellowship to work on mechanistic enzymology with Dr. W. W. Cleland at the University of Wisconsin. Following his postdoctoral fellowship, Farber returned to Penn State as an assistant professor of biochemistry and rose to the rank of associate professor with tenure by 1998. His research included work on structural movies of enzyme action, molecular evolution and mechanistic enzymology. Farber moved to the National Center for Research Resources (NCRR), part of NIH, in 2000. At NCRR, he managed a number centers and individual investigator awards in technology development and bioinformatics, a cohort of interdisciplinary research centers, as well as the $1 billion ARRA construction program. In June 2011, Farber became the director of the Office of Technology Development and Coordination at the National Institute of Mental Health (NIMH). That office is responsible for coordinating all technology development and bioinformatics activities at NIMH including common data element activities, overseeing the NIMH Data Archive, managing the NIMH component of the BRAIN Initiative, managing the Human Connectome project on behalf of the NIH Neuroscience Blueprint and also overseeing the NIMH small business program.

Gisela Felizitas Erf, Ph.D., is a Tyson Professor in Avian Immunology and director of the Cell-Isolation and Characterization Facility at the Poultry Science Center for the University of Arkansas Department of Poultry Sciences, Fayetteville, Arkansas, U.S. Erf received her Bachelor of Science and Master of Science from the University of Guelph in Ontario, Canada, before going on to receive her doctorate at Cornell University in Ithaca, New York, U.S. Her research is primarily focused on poultry immune system development and function; examination, assessment and monitoring of innate and adaptive cell-mediated responses; and immune system and nanoparticle interactions, among other pursuits. Erf has served as the chair of Graduate Students and Honors Committees since 1988 and has been a member of the Honors College faculty since 2006. She was named an Outstanding Mentor by the University of Arkansas Office of Nationally Competitive Awards in 2013 and 2014 and received the 2015 John W. White Outstanding Research Award from the University of Arkansas System Division of Agriculture.

Jan Herrmann, Ph.D., heads the nanometrology section at the National Measurement Institute Australia (NMIA). His team develops physical standards, instruments and methods for measurement at the nanometre length scale with a focus on the characterization of nanomaterials. Following a doctorate in physics from the University of Leipzig/Germany, Herrmann was a postdoctoral researcher


at the University of California, San Diego, U.S., and a research scientist at Australia’s Commonwealth Scientific and Industrial Research Organisation before joining NMIA. His current research interests include high-accuracy dimensional nanometrology and the detection, identification and quantification of nanomaterials in complex matrices. Herrmann plays a leading role in the development of documentary standards for nanotechnologies, heading the Australian delegation to the Technical Committee on Nanotechnologies of the International Organization for Standardization, chairing its Australian mirror committee, and as a member of the Steering Committee of the Versailles Project on Advanced Materials and Standards with its strong focus on prenormative research supporting standardization.

Morten Jensen, Ph.D, is an Arkansas Research Alliance Scholar and focuses his research in experimental cardiovascular surgery on creating useful solutions with sophisticated technologies. The results obtained from his work are currently used in the Food and Drug Administration guidelines for heart repair devices. He is appointed to the Danish Academy of Engineering and has won several prices for his work; he was the youngest person since 1965 to receive the prestigious “Elektroprisen” prize which is awarded by the fund Elektrofondet in the Danish Society of Engineers. Prior to joining the University of Arkansas as an associate professor of biomedical engineering, he spent six years with National Instruments (Austin, Texas, U.S.) and 10 years at the Department of Biomedical Engineering and Cardiothoracic & Vascular Surgery at the University Hospital of Aarhus, Denmark. Jensen has published extensively on his work, in scientific journals, magazines and public media. In 2015, he was only the third engineer in Denmark since 1479 to obtain the Doctor Medicinae degree, demonstrating significant clinical impact of the conducted research.

Alexander V. Kabanov, Ph.D., is a Mescal Swaim Ferguson Distinguished Professor, director of the Center for Nanotechnology in Drug Delivery and co-director of the Carolina Institute for Nanomedicine at the University of North Carolina at Chapel Hill since July 2012. Previously he was with the University of Nebraska Medical Center where he was a Parke-Davis Professor of Pharmaceutical Sciences and director of the Center for Drug Delivery and Nanomedicine, which he founded in 2004. Kabanov received his doctorate in chemical kinetics and catalysis in 1987 at Moscow State University, U.S.S.R. He has conducted pioneering research on polymeric micelles, DNA/polycation complexes, block ionomer complexes and nanogels for delivery of small drugs, nucleic acids and proteins that considerably influenced current ideas and approaches in drug delivery and nanomedicine. He co-founded Supratek Pharma, Inc., which develops therapeutics for cancer and Neuro10-9, Inc. focusing on diseases of the central nervous system (CNS). He founded the Nanomedicine and Drug Delivery Symposium series and co-chaired the Gordon Research Conference on Drug Carriers in Medicine and Biology (2006). He is a recipient of Lenin Komsomol Prize (1988), Russian “Megagrant” (2010), elected member of Academia Europaea - The Academy of Europe (2013), and fellow of American Institute for Medical and Biological Engineering’s College of Fellows


(2014), among other distinctions. He was a director of the U.S. NIH Center of Biomedical Research Excellence (CoBRE) “Nebraska Center for Nanomedicine” (2008-2012) and currently is a director of the Carolina Cancer Nanotechnology Training Program sponsored by NCI and a director of the Laboratory of Chemical Design of Bionanomaterials, which he founded at Moscow State University in 2010 with the Megagrant support.

Dmitry A. Nedosekin, Ph.D., is a research associate at the Philips Classic Laser and Nanomedicine Laboratories of the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences in Little Rock, Arkansas, U.S. He has a wide range of scientific interests in the field of biomedical optics and biophotonics including in vivo sensors, microscopy, cancer research and nanotechnology applications for health care. Nedosekin received his Bachelor of Science, Master of Science and doctorate from M.V. Lomonosov Moscow State University in Moscow. He has also served as a visiting scientist at Philipps-Universität Marburg in Marburg, Germany, and worked as a postdoctoral fellow at the Philips Classic Laser and Nanomedicine Laboratories at the University of Arkansas for Medical Sciences. His most recent work has included designing clinical prototypes of photoacoustic system for noninvasive enumeration of melanoma circulating tumor cells in human blood vessels and the development of novel nanotechnology based contrast agents for drug delivery, photothermal therapy, cancer treatment and SERS-enhanced Raman microscopy.

Anil Patri, Ph.D., serves as the director of the NCTR-ORA Nanotechnology Core Facility at the U.S. Food and Drug Administration and directs regulatory science research and collaborates with other centers and agencies. He also serves as the chairman of the Nanotechnology Task Force at FDA. Prior to joining FDA in August 2014, Patri served as the deputy director and principal scientist of the Nanotechnology Characterization Laboratory (NCL) at the Frederick National Laboratory for Cancer Research. In a decade-long tenure at NCL, he assisted collaborators from industry and academia toward clinical translation of nanomedicines, many currently in clinical trials. He led a collaborative multidisciplinary team of scientists at NCL and oversaw 85 projects through preclinical assessment that included extensive characterization, in vitro biocompatibility and in vivo pharmacokinetics, safety and efficacy studies on different nanomaterial platforms intended for drug delivery, gene delivery and imaging. From 2006-2014, he served as a guest scientist at NIST and helped co-develop the first nano-sized gold reference material standards and standard protocols through ASTM. Patri served as a research faculty at the University of Michigan Medical School, Center for Biologic Nanotechnology, and developed targeted drug delivery and imaging agents. He serves on many review panels, advisory and editorial boards. He pursued graduate work on Dendrimers and earned a doctorate in chemistry from the University of South Florida followed by postdoctoral training at the University of Michigan. He worked at Astra Zeneca and served as a lecturer in chemistry prior to his research career.


Anna Radominska-Pandya, Ph. D., currently serves as a professor in the department of biochemistry and molecular biology at the University of Arkansas for Medical Sciences (UAMS). She received her master’s degree from the University of Warsaw and her doctorate from the Institute of Biochemistry and Biophysics, Polish Academy of Sciences in Warsaw, Poland. She completed her postdoctoral training in molecular biology at Ohio State University in Columbus, Ohio. During her time at UAMS, Radominska-Pandya has received 10 R01 grants from the NIH and numerous other awards. She has published 160 papers in peer-reviewed journals, in addition to 11 book chapters and 173 abstracts, and nine issued and provisional patents. Radominska-Pandya is also a member of the UAMS Nanomedicine Center where she is the leader of ongoing collaborative research in the area of nano-genetics. She has been a member of NIH review panels since 1993, and served as chair of the NIH Member Conflicts: Hepatobiliary Pathophysiology, Toxicology and Pharmacology Review Panel in 2009. She maintains membership in the American Society for Biochemistry and Molecular Biology, American Society for Pharmacology and Experimental Therapeutics, American Association for the Study of Liver Diseases, International Society for the Study of Xenobiotics, and Iota Sigma Pi. She is reviewer for 15 journals and serves on the editorial board of two journals. Recently, she was selected an editor-in-chief for Drug Metabolism Review. Over the past two decades, Radominska-Pandya has been one of the leading investigators in the area of UGTs and glucuronidation.

Cristina Sabliov, Ph.D., is a professor in the biological and agricultural engineering department at Louisiana State University (LSU). Sabliov is leading an internationally renowned research program in the field of nanotechnology, specifically focused on polymeric nanoparticles designed for delivery of bioactive components for improved food quality and human health. Sabliov is a recognized national and international leader in nanotechnology as indicated by her funding record (PI and Co-PI on grants with a total exceeding $20 million), publications (49 peer-reviewed publications) and by her presence at major events sponsored by the Food and Drug Administration, National Institutes of Health and U.S. Department of Agriculture. She is currently serving on the Institute of Food Technologists Food Nanoscience Advisory Panel and she is the chair of the International Society for Food Applications of Nanoscale Sciences. For her significant contribution to the field, Sabliov has received numerous awards over the years such as the LSU Distinguished Professor Award (2015), ASABE New Holland Research Award (2011), LSU Ag Center Rogers Award (2010), LSU Gamma Sigma Delta Research Award of Merit (2010), and the Tiger Athletic Foundation Undergraduate Teaching Award (2007, 2013). Through her research and teaching, Sabliov is determined to address the multiple challenges and many opportunities at the interface of bioengineering and nanotechnology, and to contribute significantly to the safe application of nanotechnology in food, agriculture and health.


Justin Sanchez, Ph.D., joined DARPA as a program manager in 2013 to explore neurotechnology, brain science and systems neurobiology. Before coming to DARPA, Sanchez was an associate professor of biomedical engineering and neuroscience at the University of Miami and a faculty member of the Miami Project to Cure Paralysis. He directed the Neuroprosthetics Research Group, where he oversaw development of neural-interface medical treatments and neurotechnology for treating paralysis and stroke, and for deep brain stimulation for movement disorders, Tourette’s syndrome and Obsessive-Compulsive Disorder. Sanchez has developed new methods for signal analysis and processing techniques for studying the unknown aspects of neural coding and functional neurophysiology. His experience covers in vivo electrophysiology for brain-machine interface design in animals and humans where he studied the activity of single neurons, local field potentials and electrocorticogram in the cerebral cortex and from deep brain structures of the motor and limbic system. He is an elected member of the Administrative Committee of the IEEE Engineering in Medicine and Biology Society. He has published more than 75 peer-reviewed papers, holds seven patents in neuroprosthetic design and authored a book on the design of brain-machine interfaces. He has served as a reviewer for the NIH Neurotechnology Study Section, Department of Defense’s Spinal Cord Injury Research Program and the Wellcome Trust, and as an associate editor of multiple journals of biomedical engineering and neurophysiology. Sanchez holds Doctor of Philosophy and Master of Engineering degrees in biomedical engineering, and a Bachelor of Science degree in engineering science, all from the University of Florida.

John P. Shock, M.D., is the founding director of the Jones Eye Institute and Distinguished Professor Emeritus at the University of Arkansas for Medical Sciences (UAMS). Shock joined the faculty at UAMS after retiring from the military as a colonel in 1979. During his military career, he invented several ophthalmic surgical instruments to include the J. Shock Phacofragmenter, which removed cataracts using ultrasonic fragmentation and irrigation. This device helped to revolutionize cataract surgery worldwide by allowing the surgical wound to be reduced in size from 13mm to 3mm. After joining the COM/UAMS as professor and chairman of the department of ophthalmology, he subsequently raised philanthropic gifts to build the Harvey & Bernice Jones Eye Institute in 1994 and the Pat Walker Tower in 2004. In 2010, the Leland and Betty Tollett Retinal and Ocular Genetic Center was constructed and seven endowed chairs were established. Shock has held a number of UAMS and College of Medicine leadership positions to include interim dean (2000-2002) and executive vice chancellor (2002-2009). His awards include the College of Medicine Distinguished Service Award and the Arkansas Caduceus Club Distinguished Faculty Award. In 2009, he was the guest of honor of the annual meeting of the American Academy of Ophthalmology. From the military, he was awarded the Legion of Merit and the Meritorious Service Medal, and in 2013 he was inducted into the Arkansas Military Veterans Hall of Fame. In 2015, he was awarded a Lifetime Achievement Award by the medical community sponsored by Arkansas Business.


Zhong Lin (ZL) Wang, Ph.D., is the Hightower Chair in Materials Science and Engineering and Regents’ Professor at Georgia Tech. Wang has made original and innovative contributions to the synthesis, discovery, characterization and understanding of fundamental physical properties of oxide nanobelts and nanowires, as well as applications of nanowires in energy sciences, electronics, optoelectronics and biological science. His discovery and breakthroughs in developing nanogenerators established the principle and technological road map for harvesting mechanical energy from the environment and biological systems for powering personal electronics. Wang coined and pioneered the field of piezotronics and piezo-phototronics by introducing a piezoelectric potential gated charge transport process to fabricating new electronic and optoelectronic devices. This breakthrough in redesigning CMOS transistors has important applications in smart MEMS/NEMS, nanorobotics, human-electronics interfaces and sensors. Wang was elected as a foreign member of the Chinese Academy of Sciences in 2009, member of European Academy of Sciences in 2002, fellow of American Physical Society in 2005, fellow of AAAS in 2006, fellow of Materials Research Society in 2008, fellow of Microscopy Society of America in 2010, fellow of Royal Society of Chemistry and fellow of the World Innovation Foundation in 2002. He has received numerous awards, including the 2015 Thomas Routers Citation Laureate award, 2014 World Technology Prize in Materials, 2014 the James C. McGroddy Prize for New Materials from the America Physical Society, 2013 ACS Nano Lectureship award, 2011 MRS Medal from the Materials Research Society and is forecast as a likely recipient of the Nobel Prize in physics.

Frank Weichold is director for the Office of Critical Path and Regulatory Science Initiatives in the Office of the Chief Scientist and the Office of the Commissioner for the Food and Drug Administration. He also chairs the FDA Senior Science Council and he represents FDA at the Maryland Life Science Advisory Board. The expertise he brings to the regulatory agency builds on his ability to advance, coordinate and integrate scientific resources for FDA by addressing mission-critical scientific regulatory challenges in a global environment. The FDA Centers of Excellence in Regulatory Science and Innovation (CERSI) network is being built under Weichold’s leadership in collaboration with academic institutions to leverage scientific expertise, resources and capacity toward FDA’s mission. He was leading strategic partnership arrangement and value generation at the agency, including intellectual property development and technology transfer while on detail as the director of the Office of Regulatory Science and Innovation. Weichold’s experience includes execution of strategic and operational initiatives across the sciences’ value chain. Weichold has led the development of international collaborations and public/private partnerships for discovery and early medical product development, implemented global operating and development models and executed large-scale business model transformations. He has accumulated more than a decade of industrial research and medical product development experience while leading teams in clinical pharmacology, DMPK, as a director at MedImmune LLC, and AstraZeneca. As a tenured professor in the University of Maryland system, he developed and managed independent research programs and trained graduate students. He also held faculty positions at the University of Maryland Biotechnology Institute to study signal transduction pathways that affect immune responses, as well as at the Humboldt University, Berlin, Germany, to teach and study microbial immune modulation.


WEDNESDAY, DECEMBER 2, 2015ABSTRACTS


CREATIVITÉ SANS FRONTIÈRES

Harold Kroto

Florida State University, Florida, U.S.

Pasteur claimed that, “Fortune favours only the prepared mind.” Simply stated and oft-quoted, but the question is of course: How does one actually “prepare” one’s mind to be creative? This presentation examines all aspects of creativity, in general, providing evidence that to be successful in any walk of life the most important thing that we must develop is an openness to ideas and concepts from every corner—often a seemingly unlikely corner—of the intellectual and cultural environment from the arts to the sciences. If one examines a wide range of examples of creativity, one finds that there are common factors wherever breakthroughs are made in science, technology, the arts, the media, etc. The evidence is that creativity invariably involves a synthesis in which contributing factors which might, a priori, have seemed disparate are conflated to produce something totally new and novel. From an educational perspective, a key aim of education must be to unlock the creative potential of all our young people and this means that an educator must find ways of stimulating and encouraging the intellectual curiosity that all small children possess. All children possess curiosity from the moment they are born and that as students it must be maintained and nurtured to be open to a wide range of subjects and crossing boundaries between subjects if they are to be creative in adult life.

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PLENARY ABSTRACTS


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CREATIVITÉ SANS FRONTIÈRES


BIOANALYTICS USING SINGLE PLASMONIC NANOSTRUCTURES

Wolfgang Fritzsche

Leibniz Institute of Photonic Technology (IPHT), Jena, Germany

Novel requirements for bioanalytical methods emerge due to trends, such as personalized medicine or pathogen detection in environment and food. Here, innovative tools for diagnostics are needed, to be used outside of dedicated laboratories with less qualified personnel and minimal costs. Plasmonic nanostructures promise to provide sensing capabilities with the potential for ultrasensitive and robust assays in a high parallelization, without the need for marker. Upon the binding of molecules, the localized surface plasmon resonance (LSPR) of these structures are changed, and can be used as sensoric readout. Here the use of individual nanostructures (such as gold nanoparticles) for the detection and manipulation of biomolecules (e.g. DNA) based on optical approaches is presented [1].

Holes in a Cr layer present an interesting approach for bioanalytics. They are used to detect even single plasmonic nanoparticles as labels or to sense the binding of DNA on these particles. This hybrid system of hole and particle allows for simple (just using RGB-signals of a CCD [2]) but a highly sensitive (one nanoparticle sensitivity) detection. Moreover, the binding of a molecular layer around the particles can be detected using spectroscopic features of just an individual particle [3].

The change in LSPR of individual metal nanoparticles is utilized to monitor the binding of DNA directly or via DNA-DNA interaction. The influence of different size (length) as well as position (distance to the particle surface) is thereby studied [4] using a dark-field approach developed a century ago [5]. The established serial approach is now further developed into a parallel readout using imaging spectrometric sensing based on interferometry and Fourier transformation.

Besides sensing, individual plasmonic nanostructures can be also used to manipulate biomolecular structures, such as DNA. Attached particles can be used for local destruction [6] or cutting as well as coupling of energy into (and guiding along) the molecular structure [7]. The resonance of these particles can not only be manipulated by their inherent properties (material, geometry) or their surrounding, but also by interferometric approaches [8].References

[1] A. Csaki, T. Schneider, J. Wirth, N. Jahr, A. Steinbrück, O. Stranik, F. Garwe, R. Müller and W. Fritzsche, Philosophical Transactions A 369, 3483-3496 (2011).

[2] N. Jahr, N. Hädrich, M. Anwar, A. Csaki, O. Stranik and W. Fritzsche, Int J Env Anal Chem 93, 140-151 (2013).

[3] N. Jahr, M. Anwar, O. Stranik, N. Hädrich, N. Vogler, A. Csaki, J. Popp, W. Fritzsche. J Phys Chem C 117, 7751-7756 (2013).

[4] T. Schneider, N. Jahr, A. Csaki, O. Stranik and W. Fritzsche, J Nanopart Res 15, 1531 (2013).

[5] T. Mappes, N. Jahr, A. Csaki, N. Vogler, J. Popp, W. Fritzsche. Angew Chem Int Ed 51, 11208-11212 (2012).

[6] A. Csaki, F. Garwe, A. Steinbrück, G. Maubach, G. Festag, A. Weise, I. Riemann, K. König and W. Fritzsche, Nano Letters 7 (2), 247-253 (2007).

[7] J. Wirth, F. Garwe, G. Haehnel, A. Csaki, N. Jahr, O. Stranik, W. Paa and W. Fritzsche, Nano Letters 11 (4), 1505-1511 (2011).; J. Toppari, J. Wirth, F. Garwe, O. Stranik, A. Csaki, J.

Bergmann, W. Paa, W. Fritzsche, ACS Nano 7, 1291-1298 (2013); J. Wirth, F. Garwe, J. Bergmann, W. Paa, A. Csaki, O. Stranik, W. Fritzsche. Nano Letters 14, 570-577 (2014).

[8] J. Wirth, F. Garwe, R. Mayer, A. Csaki, O. Stranik, W. Fritzsche: Nano Letters 14, 3809-3816 (2014).

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BIOANALYTICS USING SINGLE PLASMONIC NANOSTRUCTURES


POLYMERIC MICELLES – A TRANSFORMATIVE TECHNOLOGY AT THE CLINICAL STAGE

Alexander Kabanov

Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina, U.S.

Polymeric micelle drug carriers were invented a quarter of century ago [1]. Today this technology has reached a clinical stage. Nearly a dozen of drug candidates based on polymeric micelles undergo clinical trials and one product, Genexol-PM, a polymeric micelle paclitaxel, was approved for cancer therapy in South Korea [2]. The value proposition of currently developed polymeric micelle drugs include increased drug solubility, increased extravasation and targeting to disease sites (e.g. tumors) as well as increased drug activity with respect to multidrug resistant cancers and cancer stem cells (CSC). One class of polymeric micelles is small aggregates (10 to 100 nm) formed by amphiphilic block copolymers. Hydrophobic drug molecules incorporate in polymeric micelles through cleavable covalent bonds or non-covalent interactions. Latest developments in this field include poly(2-oxazoline)-based polymeric micelles that can carry unprecedented high loading of hydrophobic drugs, such as paclitaxel, as well as blends of several insoluble drugs [3].

Such formulations have much lower toxicity compared to conventional formulations, which use high amounts of unsafe excipients to dissolve poorly soluble drugs. Consequently, novel polymeric micelle formulations can be administered at much greater doses and are more efficient in killing cancer cells. Another class of polymeric micelles incorporates charged drug molecules and macromolecules by forming an electrostatic complex with ionic block copolymers. In this format the incorporated molecules entrap into the polyion complex cores of micelles where they are protected from the biological environment by non-ionic water-soluble polymeric micelle shell. Upon reaching the target destination the micelles disintegrate and released their payload. This technology, originally developed for antisense oligonucleotides [4], is now being used with chemotherapeutic agents, pDNA, siRNA and proteins. For example, extensive studies focus on the use of such systems for delivery of therapeutic enzymes (nanozymes) to the brain and other disease sites. In selected cases the nanozymes or are loaded into macrophages, which safely transport them, and released at the sites of inflammation during disease [5]. Moreover, the macrophages were shown to transduce the nanozyme particles as well as deliver genes into the host cells at the disease site [6]. The proof of the principle has been obtained using animal models of stroke, hypertension, Parkinson’s disease, eye inflammation, influenza virus infection, spinal cord injury and other diseases.

Recent work supported by NIH (1U54CA198999, 1U01CA198910, U01CA151806, R01CA184088, R21NS088152, R01NS051334, R01CA89225, P20RR021937), NC TraCS (4DR11404), NSF (DMR1121107), DTRA (HDTRA1-09-14-FRCWMD-BAA), Rettsyndrome.org (HeART Award #3112) and Ministry of Education and Science of Russian Federation (11.G34.31.0004).References

[1] H. Bader et al. Angew. Macromol. Chem. 1984, 123/124:457; A. Kabanov et al. FEBS Lett. 1989, 258:343; M. Yokoyama et al. Cancer Res. 1990, 50:1693.

[2] M. Yokoyama et. al. J. Exp. Clin. Med. 2011, 3:8.

[3] R. Luxenhofer et al. Biomaterials 2010, 31:4972; Y. Han et al. Mol. Pharmaceutics 2012, 9:2302; A. Schulz, et al. ACS Nano 2014, 8 (3), 2686–96.

[4] A. Kabanov et al. Bioconj. Chem. 1995, 6: 639; A. Harada and K. Kataoka, Macromolecules 1995, 28: 5294.

[5] A.M. Brynskikh et al., Nanomedicine 2010, 5:379-96; M.J. Haney, et al. Nanomedicine 2011, 6:1215.

[6] M.J. Haney, et al., PLoS ONE 2013, 8(4): e61852; Y. Zhao, et al. PLoS One 2014, 9(9):e106867.

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POLYMERIC MICELLES – A TRANSFORMATIVE TECHNOLOGY AT THE CLINICAL STAGE


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WHO CARES ABOUT UNCERTAINTIES? MEASUREMENT CHALLENGES FOR NANOMATERIALS

Bakir Babic, Victoria A. Coleman, Jan Herrmann, Åsa K. Jämting, Malcolm A. Lawn

Nanometrology Section, National Measurement Institute Australia, Australia

Accurate measurements of the physical and chemical characteristics of nanomaterials and nanostructures are critical for the development of nanotechnologies, both at the scientific discovery stage and for the responsible translation of the discoveries into applications and products. Nanometrology, the science of nanoscale measurement, helps to ensure that measurements of the relevant properties are quantifiably comparable. It thus not only facilitates the design and implementation of nano-enabled functionality, but also enables the evaluation of the technology’s potential risks for human health and for the natural environment.

Some of the most relevant nanomaterial properties for such studies include the number and/or mass concentration, chemical composition, particle size distribution, agglomeration/aggregation state, surface charge and surface chemistry. Characterization of these parameters in nanoscale systems presents numerous challenges, particularly in application-relevant matrices, such as tissue, physiological fluids, food or environmental systems. No single measurement technique or instrument is capable of addressing all of these challenges and usually a combination of different measurement methods should be applied. We illustrate some of the differences and complementarities of commonly used techniques using practical examples.

Our efforts to provide accurate characterization of nanomaterials in application-relevant matrices are underpinned by nanoscale dimensional measurements that are traceable to the SI metre. This is particularly important for emerging regulations for nanomaterials that rely on measurement-based definitions. In this context, we discuss the concept of measurement traceability at the nanoscale and highlight the critical role of reference materials and documentary standards.


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WHO CARES ABOUT UNCERTAINTIES? MEASUREMENT CHALLENGES FOR NANOMATERIALS


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TRIALS ON SYSTEMIC DELIVERY OF CANCER NANOMEDICINE VIA TARGETED NANOCOMPLEXES

Esther H. Chang

Department of Oncology, Georgetown University Medical Center, Washington, D.C., U.S.

A tumor-targeting nanodelivery system has been developed comprising a self-assembled, biodegradable, cationic liposomal nanoparticle, which bears targeting molecules that home to receptors, such as the transferrin receptor, on the surface of tumor cells. When systemically administered, this nanocomplex can specifically deliver gene medicine, including plasmid DNA, si/miRNA and ODNs, as well as imaging contract agents, small molecule therapeutic agents and cytotoxic chemotherapeutic agents, not only to primary tumors, but also to metastases. Use of this nanocomplex in delivering various gene medicines has been shown to dramatically enhance the tumor response to radiotherapy and chemotherapy in a number of mouse models of human cancers, resulting in long-term tumor elimination and lifespan prolongation. CSCs are implicated in recurrence and resistance in human cancers. We have also demonstrated that the significant efficacies observed are attributed, at least in part, to CSC-targeting.

The prototype of this platform technology, the nanocomplex carrying the normal p53 gene (SGT-53) has completed Phase Ia and Ib clinical trials in patients with advanced solid tumors. It was well tolerated at therapeutically relevant dosages. More significantly, even when SGT-53 was tested as a single agent, >70% of patients demonstrated stable disease or better. Two Phase II trials assessing the efficacy of the agent in combination with standard therapies in pancreatic cancer and glioblastoma patients are ongoing. In addition, a Phase I trial of SGT-53 in pediatric patients with recurrent solid tumors is also underway. A nanocomplex carrying RB94, a tumor suppressor gene, has also been evaluated in a Phase I trial.

WORKSHOP ABSTRACTS

WORKSHOP 1 – STRATEGIES FOR TARGETED DELIVERY OF NANOPARTICLES AND NANOSENSORS


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TRIALS ON SYSTEMIC DELIVERY OF CANCER NANOMEDICINE VIA TARGETED NANOCOMPLEXES


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ENGINEERING POLYMER-COATED GOLD NANOCAGES FOR TARGETED DELIVERY AND CONTROLLED RELEASE OF THERAPEUTIC AGENTS

Jingyi Chen

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas, U.S.

Drug delivery systems with targeted capability and on-demand controlled release mechanisms are particularly appealing for designing optimal medications in many disease treatments. One of such systems consists of polymer-coated gold nanocages (AuNCs) that are capable of converting light into heat and triggering the release of the encapsulated therapeutics. The release kinetics is dependent on the noncovalent binding affinity of the polymer-drug complexes. In this presentation, I will discuss two examples: poly(ethylene glycol)- (PEG-) coated AuNCs and polydopamine- (PDA-) coated AuNCs. The former (PEG-coated AuNCs) was particular suited for the delivery of hydrophobic porphyrin-containing photosensitizers. The latter (PDA-coated AuNCs) was applicable to deliver a hydrophilic antibiotic daptomycin. In both cases, the photothermal effect of AuNC can initiate an instantaneous release, and thus control of the release kinetics, demonstrating on-demand drug release. The surface of these polymer-coated AuNCs can be readily functionalized with specific moieties for targeting biomarkers at the pathological sites. Further utilizing the optical properties of AuNCs, these systems can achieve theranostics through diagnosis via AuNC contrast-enhanced molecular imaging and multi-modal treatment via photodynamic-, photothermal- and chemo-/antibiotic- therapies. An example will be discussed for the treatment of intrinsically resistant biofilm infections, demonstrating targeted, photothermal and antibiotic therapeutic synergy.


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ENGINEERING POLYMER-COATED GOLD NANOCAGES FOR TARGETED DELIVERY AND CONTROLLED RELEASE OF THERAPEUTIC AGENTS


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DELIVERY OF GENES AND DRUGS INTO PANCREATIC AND BREAST CANCER CELLS BY MULTIFUNCTIONAL NANOPARTICLES

Anna Radominska-Pandya1 and Alexandru S. Biris2

1Department of Biochemistry and Molecular Biology, UAMS, Little Rock, Arkansas, U.S.; 2Applied Science Department, Center of Nanotechnology, UALR, Little Rock, Arkansas, U.S.

Drug-metabolizing enzymes, such as human UDP-glucuronosyltransferases (UGTs), are involved in the metabolism and detoxification of both drugs and endogenous compounds that regulate growth, homeostasis and differentiation of cancer cells. We propose the use of nanostructural materials as carriers for the delivery of UGT genes and selected nontoxic drugs into pancreatic and breast cancer cells. Recently, we have developed an efficient method of binding plasmids DNA to nanoparticles and investigated the transfer of UGTs into cancer cells. We used gold nanotubes (20 µg/ml) attached to a UGT expression plasmid to form the active bio-nano systems. Specific in-vitro delivery of these nanosystems by using growth factors was also proved. The incubation of gold/UGT particles with both types of cells for 72 hours resulted in phenotype changes in the cells and eventually death as measured by Caspase 3 activity. Moreover, treatment with several drugs conjugated into nanoparticles results in decreased cell proliferation and death. Examining the role of human UGTs and natural drugs in cancer cell homeostasis with the application of nanotechnology is a novel approach to cancer research.

DoD-W81XWH1110795 to AR-P and AB and UAMS TRI ABCRP funds to AR-P


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DELIVERY OF GENES AND DRUGS INTO PANCREATIC AND BREAST CANCER CELLS BY MULTIFUNCTIONAL NANOPARTICLES


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ASTM INTERNATIONAL COMMITTEE E56 ON NANOTECHNOLOGY–CELEBRATING 10 YEARS OF ADVANCEMENT

Kate Chalfin

ASTM International, Conshohocken, Pennsylvania, U.S.

Formed in 2005, ASTM International Committee E56 has been at the forefront of standards development addressing nanotechnology. From standards addressing the safety of those working with nanomaterials, to standards outlining education guidelines for current and future nanotechnology professionals, to standards on the detection and identification of manufactured nanomaterials in consumer goods, Committee E56 members have been working to address the standards needs of consumers, industry and government agencies over the past 10 years. ASTM International is a globally recognized leader in the development and delivery of voluntary consensus standards. Today, over 12,000 ASTM standards are used around the world to improve product quality, enhance health and safety, strengthen market access and trade, and build consumer confidence. Our leadership in international standards development is driven by the contributions of our members: more than 30,000 of the world’s top technical experts and business professionals representing 140 countries. This presentation will highlight the work of Committee E56, focusing on both published standards and current working drafts, and will give an overview of ASTM International, focusing on the open consensus standards development process.

WORKSHOP 2 – BEST PRACTICES AND STANDARDS FOR NANOMATERIAL CHARACTERIZATION


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ASTM INTERNATIONAL COMMITTEE E56 ON NANOTECHNOLOGY–CELEBRATING 10 YEARS OF ADVANCEMENT


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ADVANCING REGULATORY SCIENCE AT FDA

Frank F. Weichold

Critical Path and Regulatory Science Initiatives, ORSI Office of Regulatory Science and Innovation, Office of the Chief Scientist, Office of the Commissioner, U.S. Food and Drug Administration, White Oak, Silver Spring, Maryland, U.S.

The Office of Regulatory Science and Innovation (ORSI) in the Office of the Chief Scientist (OCS) supports regulatory science research, scientific coordination and infrastructure across the FDA centers by facilitating and establishing high-quality scientific collaborations, supporting the latest scientific advances and technologies, and building academic Centers of Excellence in Regulatory Science and Innovation (CERSI). Intramural collaborative regulatory science research across FDA centers is supported by OCS Challenge Grants and grants focused on nanotechnology (CORES), both of which are supported in part and managed by ORSI. In addition, ORSI supports FDA intramural scientific excellence and collaboration through FDA Scientific Working Groups focused on specific topics, such as genomics, biomarkers and other cutting-edge scientific areas. These working groups provide a forum for scientific exchange, visibility, collaboration and cooperation across the centers. A recently established working group, “shared resources”, seeks to leverage investments across the FDA centers to optimally utilize resources in support of specialized technical and scientific capabilities of interest to two or more centers.

Extramural programs include regulatory science research supported through the Broad Agency Announcements (BAA) for the Advanced Research and Development of Regulatory Science, which encourage submission of research proposals that address any of the nine key objectives of the FDA Advancing Regulatory Science Strategic Plan. Over 45 research projects funded both by ORSI and by centers have been awarded through this mechanism. The extramural CERSI program supports and facilitates four academic centers conducting research, education and training in regulatory science. These CERSIs also provide a mechanism for centers to interact with academic colleagues conducting cutting-edge research in areas of interest to FDA. ORSI manages the FDA Technology Transfer Program through coordination of Research Collaboration Agreements (RCAs) and Cooperative Research and Development Agreements (CRADAs) throughout the centers, as well as managing licensing, patenting and royalty activities associated with inventions generated by FDA researchers. While in the past FDA obtained support for certain activities from the NIH Office of Technology Transfer, that office is decentralizing, and ORSI is in the process of building the capability to comprehensively support all aspects of technology transfer for FDA.


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ADVANCING REGULATORY SCIENCE AT FDA


LC/MS/MS QUANTITATION OF PARTHENOLIDE (PTL) IN PLASMA AND BONE SAMPLES FROM AML-PDX MICE AFTER I.V. INJECTION OF MSV-PTL-NANOPARTICLES

Zaineb A F Albayati1, Hongliang Zong2, Siddhartha Sen2, Guodong Zhang3, David G. Gorenstein4, Xuewu Liu3, Mauro Ferrari3, Peter A. Crooks1, Gail J. Roboz2, Haifa Shen3, and Monica L. Guzman2

1Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.; 2Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, New York, U.S.; 3Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, U.S.; 4Institute of Molecular Medicine, University of Texas-Houston Medical School, Houston, Texas, U.S.

Acute myelogenous (myeloid) leukemia (AML) is a cancer of the myeloid line of blood cells. Parthenolide (PTL), a naturally occurring sesquiterpene isolated from Tanacetum parthenium (feverfew), is highly effective for induction of cell death of primary human AML specimens. A multistage vector (MSV) nanoparticle system was designed as a drug delivery system in which the end goal was to achieve PTL release in the bone marrow in a chemically intact form. The aim of this study was to determine the concentration of PTL in plasma and femur bone samples obtained from patient-derived AML-xenograft (PDX) mice after a single i.v. injection of MSV-PTL nanoparticles at a dose of 2.5 mg/kg of PTL. Following i.v. dosing of the MSV-PTL nanoparticle system, PTL was detected in bone samples within 1 hour with an average concentration of 375.0 ± 14.7 nM. However, no PTL was detected in the plasma at the 1 hour time point indicating that there was likely no degradation of the MSV-PTL nanoparticles to release PTL in plasma. The data are consistent with selective targeting of the bone and in vivo release of PTL from the MSV-PTL nanoparticles in bone tissue, since measurable levels of PTL were observed in the femur bones of mice 1 hour after a single i.v. bolus injection of MSV-PTL nanoparticles.

PARTICLE SIZE CHARACTERIZATION STUDIES OF TITANIUM DIOXIDE AND ZINC OXIDE NANO PARTICLES IN COMMERCIAL SUNSCREENS

Venu Gopal Bairi1, Jin-Hee Lim1, Thilak Mudalige1, Sean W. Linder2, and Andrew Fong1

1U.S. Food and Drug Administration, Office of Regulatory Affairs, Arkansas Regional Laboratory, Jefferson, Arkansas, U.S.; 2 U.S. Food and Drug Administration, Office of Regulatory Affairs, Office of Regulatory Science, Jefferson, Arkansas, U.S.

There is a tremendous increase in the usage of sunscreens due to concerns about UV exposure. Organic and inorganic minerals are used as UV filters in sunscreens. The primary mineral filters employed in the majority of commercial sunscreens include nanosized TiO2 and ZnO. The toxicity of these nanoparticles is not completely understood in humans and the environment. There is an immediate necessity for developing analytical techniques, which can be used for isolation and characterization of nanoparticles in sunscreens. Since sunscreen contains up to 75% organic materials, isolation of these mineral particles from sunscreens poses to be a greater problem. This study was focused on the isolation of nanoparticles by using several different techniques, such as extraction with various solvents, plasma ozonolysis and filtration. Among all the isolation techniques, extraction with tetrahydrofuran solvent was found to be the most promising for isolation of mineral particles from sunscreen products. The extracted samples were analyzed by using electron microscopy (TEM and SEM), elemental analysis, dynamic light scattering, disc centrifugation, UV-Visible spectroscopy and X-ray diffraction techniques. The extract contains a mixture of both TiO2 and ZnO; therefore, bulk size characterization techniques,

POSTER PRESENTATION ABSTRACTS


such as DLS and CPS, are problematic. Elemental analysis along with electron microscopy proved to be a valuable technique for individual identity of nanoparticles.

SURFACE ENGINEERING OF OCVD COATED CONDUCTING CO-POLYMERS FOR CHEMO-RESISTIVE BIOSENSORS

Tannay Bera1†, Aaron Bandremer2, Hilal Goktas2,3, Patrick Sisco1, Andrew Fong1, Sean Linder1, Karen Gleason3, Andre Senecal4, Kris Senecal5, and Steven Torosian2*1U.S. Food and Drug Administration, Arkansas Regional Lab, Jefferson, Arkansas, U.S.; 2U.S. Food and Drug Administration, Winchester Engineering and Analytical Center, Winchester, Massachusetts, U.S.; 3Massachusetts Institute of Technology, Chemical Engineering Department, Cambridge, Massachusetts, U.S.; 4Food Protection Team, U.S. Army Natick Soldier Research, Development, and Engineering Center (NSRDEC), Natick, Massachusetts, U.S.; 5Macromolecular Sciences and Engineering Team, U.S. Army NSRDEC, Natick, Massachusetts, U.S.; †Presenting author; *Author of correspondence

Biosensors play an important role in improving the public health and food safety. Hence, there has been a national priority in developing a field deployable biosensor that can counter a pathogen outbreak or bioterrorism event. Out of several proposed biosensors, the chemo-resistive biosensors have been found to be most promising for the real-time detection of pathogens in food and water samples. Our initial work on developing a conducting polymer based chemo-resistive biosensor showed good sensitivity and selectivity. Our sensor uses oCVD (oxidative chemical vapor deposition) coated conducting co-polymers PEDOT-3TE on polypropylene substrates as the sensing unit whose resistivity changes in presence of an analyte, which in our case is a bacteria. Our present study shows that the sensitivity of the biosensor is significantly higher for a fibrous substrate than for their thin film counterparts. Moreover, the fibers with nano size diameter (D ~ 200nm) also have better binding ability to the pathogen, hence higher sensitivity compared to micro size fibers (D ~ 200 µm). This change in sensitivity is not only attributed to the higher surface area of the fibrous network but also to the nature of the co-polymers coating. Detailed electron microscopy (EM) studies indicate that the coating thickness and morphology is dependent on the substrate curvature. Furthermore, the morphology of the coating was also found to depend on the composition of the co-polymers. This work summarizes various factors and their effects on obtaining an optimized co-polymer coating for our biosensor with the aim of obtaining the best sensitivity in pathogen detection.

PHOTOACOUSTIC DETECTION OF CIRCULATING TUMOR CELLS TARGETED BY CONJUGATED GOLD NANORODS IN BREAST CANCER PATIENT BLOOD

Chengzong Cai1,2, Dmitry A. Nedesekin1, Mazen A. Juratli1,3, Mustafa Sarimollaoglu1, Yulian A. Menyaev1, Kai Carey1, Ekaterina I. Galanzha1, Laura Hutchins4, and Vladimir P. Zharov1

1Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.; 2Division of Biochemical Toxicology of National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas; U.S.; 3Department of General and Visceral Surgery, University Hospital of Frankfurt, Frankfurt am Main, Germany; 4Division of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.

Gold nanorods (GNRs) are low toxicity and strongly absorbing nanoparticles (NPs) which makes it possible to use them as high-contrast photoacoustic (PA) molecular agents for detection of low absorbing circulation tumor cells (CTCs) with integrated PA and fluorescent (for verification) flow cytometry (PAFFC). The potential of these conjugated GNRs to target CTCs in whole blood is not yet well explored. To evaluate the feasibility of usage of GNRs to detect CTCs in breast cancer blood ex vivo, GNRs were conjugated with breast cancer cell surface markers (e.g., EpCAM, Folate) with antibody and folic acid and the NP cocktail were incubated with different subtypes of breast cancer cells (ZR-75-1, MDA-MB-231) in vitro in PBS and blood. The binding sensitivity and specificity were evaluated by PAFFC. EpCAM-GNRs provided higher


sensitivity in Lumina breast cancer (ZR-75-1, 15%) compared to Basel-like breast cancer (MDA-MB-231, 5%); Folate-GNRs provided higher specificity (than EpCAM-GNRs) on the level of 30% in MDA-MB-231 and 20% in ZR-75-1. Higher sensitivity (45%) was observed in EpCAM and Folate-GNRs combination in MDA-MB-231 cell, but not in ZR-75-1. Some aggregations of GNRs were observed in both PBS and blood, which led to false positivity. Clinical trial showed much higher number of PA signals in breast cancer patients than that of volunteers. Our data indicated the high potential of conjugated GNRs being used as PA molecular contrast agents for detection of CTCs in breast cancer patient blood with PAFFC, which could be a powerful tool for CTCs research after further improvements.

BIOINSPIRED HEMOZOIN NANOCRYSTALS AS HIGH CONTRAST PHOTOACOUSTIC AGENTS FOR ULTRASENSITIVE MALARIA DIAGNOSIS

Kai A. Carey, Yulian A. Menyaev, Chenzhong Cai, Jason S. Stumhofer, Dmitry A. Nedosekin, Ekaterina I. Galanzha, and Vladimir P. Zharov

Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.

Unprecedented nanotechnological advances promise to revolutionize deadly disease diagnosis and therapy by enhancing imaging contrast and improving drug/vaccine delivery. Nevertheless, challenges still remain in treating malaria, which kills over half a million people every year. Early disease diagnosis and accurate staging are crucial for good treatment outcomes. We show here that early noninvasive (needleless) label-free diagnosis and, hence, well-timed treatment of malaria are feasible by the use of hemozoin nanocrystals as intrinsic high contrast photoacoustic (PA) agents in combination with in vivo PA flow cytometry (PAFC). Hemozoin, with the average size of 50-400 nm are created in infected red blood cells (RBCs) as a result of detoxification of the byproducts from hematophagous parasites, in particular, P. yoelii. We discuss the properties of these not yet well characterized NPs and demonstrate that they can provide very high levels of PA contrast in infected RBCs above hemoglobin background comparable to that of engineered artificial metal nanoparticles (NPs) used for targeting circulating tumor cells and bacteria. Moreover, laser-induced vapor nanobubbles around overheated hemozoin nanocrystals as a PA signal amplifier makes it possible to detect rare infected RBCs even in deep vessels that improve diagnostic speed and sensitivity. PA detection of hemozoin in combination with fluorescent detection of GFP-expressing parasites provide a detailed real-time picture of infection dynamics. Laser disruption of hemozoin containing RBCs may be used for destruction of infected cells. We are confident that natural hemozoin nanoparticles may find multiple applications in health care similar to those of metal engineered nanomaterials.

TUNING THE OPTICAL-PLASMONIC PROPERTIES OF AG/AU HYBRID NANOPARTICLES FOR SERS

Elise Chaffin, James Barr, Xiaohua Huang, and Yongmei Wang

The University of Memphis, Department of Chemistry, Memphis, Tennessee, U.S.

Noble metal nanoparticles (NPs) exhibit unique optical-plasmonic properties that make them advantageous for numerous applications. Gold nanomaterials in particular have been employed in imaging, sensing and therapeutic applications due to their simple conjugation with various biomarkers as well as their biocompatibility and low reactivity. As a result of the large electric fields generated at the surfaces of gold (Au) and silver (Ag) NPs by the localized surface plasmon resonance (LSPR) of the conduction band electrons, Ag and Au NPs greatly enhance the signals of Raman scattering by adsorbed molecules. The LSPR in Ag NPs is more intense than in Au NPs and, consequently, Ag NPs typically provide stronger


surface enhanced Raman scattering (SERS) signals. However, Ag NPs lack the chemical stability and biocompatibility of their Au counterparts and typically exhibit their most intense LSPR properties at wavelengths much shorter than the optimal spectral region for certain biomedical applications. To overcome these issues, various Ag/Au hybrid NPs have been synthesized. In this study, the discrete dipole approximation was employed to model the LSPR spectra and near-field enhancements of Ag-Au core-shell NPs along with Ag/Au alloyed NPs to evaluate the effects of NP composition on these properties.

LOCAL AND SYSTEMIC ADAPTIVE IMMUNE RESPONSES TO IRON OXIDE NANOPARTICLE-CONJUGATED ANTIGEN

Gisela F. Erf1, Hyeonmin Jang1, Olfat Alaamri1, Kristen Byrne1, Daniel Falcon1, and Zoraida Aguilar2

1University of Arkansas, Division of Agriculture, Department of Poultry Science, Fayetteville, Arkansas, U.S.; 2Zystein, LLC, Springdale, Arkansas, U.S.

Using the dermis (pulp) of growing feathers (GF) as a dermal test-tissue together with blood sampling, we monitored cellular and humoral immune responses in chickens immunized with three different formulations of mouse IgG test-antigen (T-Ag). For immunization, T-Ag was injected i.m. in two groups of chickens either alone, mixed with Alum adjuvant or conjugated to iron oxide nanoparticles (10 nm). Group 1 was immunized at 7 weeks; Group 2 at 7 and 11 weeks (n = 18 chickens/Group). Antibody production (IgM, IgG) to T-Ag was monitored for 4 weeks following both the primary and secondary i.m. immunizations. To examine the local effector response to T-Ag, T-Ag was injected into 20 GF per bird (10 μL/GF) on Day 10 (Group 1) or Day 5 (Group 2) post-primary or secondary immunization, respectively, and GF collected before and 0.25, 1, 2, 3, 4, 5 and 7 days post-injection. Collected GF were used to determine leukocyte infiltration (heterophils, macrophages, B cells and T cell subsets) by flow cytometry and cytokine-expression (interleukin (IL)-1, -4, -6, -10, -21 and interferon-gamma) by quantitative RT-PCR. Cell population- and cytokine-analysis revealed temporal, qualitative and quantitative differences (P < 0.05) in leukocyte-infiltration between immunization treatments and between innate, effector-primary and effector-memory responses to T-Ag. Similarly, ELISA also revealed temporal, qualitative and quantitative differences (P < 0.05) in the humoral responses to T-Ag following the different primary/secondary i.m. immunizations. Minimally invasive, non-terminal procedures, such as sampling of injected GF and blood, provide unique insight into cellular and humoral immune responses and bioactivities of nanoparticles.

CONDUCTING CO-POLYMERS BASED CHEMIRESISTIVE ENVIRONMENTAL BIOSENSORS FOR REAL-TIME PATHOGEN DETECTION

Stephen Torosian1, Aaron Bandremer1, A. Hebert1, Hilal Goktas1,2, Tanmay Bera3, and Karen K. Gleason2

1U.S. Food and Drug Administration, Winchester Engineering and Analytical Center, Winchester, Massachusetts, U.S.; 2Massachusetts Institute of Technology, Chemical Engineering Department, Cambridge, Massachusetts, U.S.; 3U.S. Food and Drug Administration, Arkansas Regional Lab, Jefferson, Arkansas, U.S.

Pathogens can cause outbreak of infectious diseases in both animals and humans. Their timely detection in food and water is therefore essential for health care and public safety and has remained one of the research priorities at the FDA. The ultimate goal is to develop a field deployable environmental biosensor that is quick and simple to be used and yet can detect the slightest of pathogen contamination in food and water samples. The aim is also to achieve specificity by identifying the virulence in actual field applications where conventional, sophisticated, heavy machineries are hard to get access to. During the past several years, we have designed and developed a chemiresistive biosensor that holds the potential for such an application. We use oCVD (oxidative chemical vapor deposition) co-polymerization of 3,


4-ethylenedioxythiphene (EDOT) and 3-thiopheneethanol (3-TE) to obtain a conducting active layer as the primary sensing unit. The sensor works on the principle that the resistivity of the conducting co-polymer is altered when anchored with specific antibody and challenged with a pathogen, such as E. coli. The coating substrates were varied to obtain the desired surface area (hence sensitivity) and robustness as required for the applications, and the co-polymer coatings could be suitably modified to achieve the desired anchoring and selectivity. The sensor design allows tunable, sensitive and selective detection pathogens and can screen large volumes of samples, which have been unprecedented for most portable biosensors. Our studies, therefore, pave the way forward for a real-time, field deployable biosensor that is simple yet effective for a wide range of applications and has the potential to be used in managing pathogen outbreaks in the near future.

SILVER-NANOPARTICLE EXPOSURE-INDUCED ALTERATION OF APOPTOSIS-ASSOCIATED PROTEINS IN AN IN VITRO MODEL OF THE BLOOD-BRAIN BARRIER

Qiang Gu, Ph.D.1; Susan Lantz-McPeak1; Elvis Cuevas1; Syed F. Ali1; Merle G. Paule1; Jyotshna Kanungo1; Yongbin Zhang2; and Victor Krauthamer3

1Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, U.S.; 2Nanotechnology Core Facility, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, U.S.; 3Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, U.S.

Emerging nanoparticle (NP)-based materials are being increasingly introduced into consumer products. While the advantages and benefits of using NPs can be easily recognized and appreciated, their potential adverse effects are often unknown due to a lack of thorough investigation and consumer experience. Since available evidence suggests that certain NPs do possess unwanted cytotoxicity, examination of such NP-associated effects is needed to better characterize their risk/benefit profiles. In the present study, primary cultures of rat brain micro-vessel endothelial cells were utilized as an in vitro model of the blood-brain barrier and were exposed to 20 nm diameter citrate-coated silver-NPs (AgNPs) for 24 hours. AgNP-induced cytotoxicity was determined by dose-dependent increase in cell membrane leakage (LDH assay) and mitochondrial dysfunction (XTT assay). Proteins were extracted from AgNP-treated (10 µg/mL) and control cultures and then subjected to antibody microarray analysis. Among more than two dozen apoptosis-associated proteins evaluated, 14 were significantly down-regulated while three showed significant up-regulation, indicating that these proteins may play important roles in AgNP-induced toxicity/cell death. These microarray results were further validated using capillary-electrophoresis based immunoblotting (Simple-Western) analyses. The changes in expression of apoptosis-associated proteins may represent molecular signatures or “biomarkers” of NP-induced cytotoxicity and identifying such signatures and the proteins that contribute to them may aid in the future evaluation of the potential cytotoxic effects associated with NP-exposure.

Supported by NCTR Protocol E746001.


PHOTOSWITCHABLE NON-FLUORESCENT NANOPARTICLES FOR TRACKING INDIVIDUAL TUMOR AND BACTERIAL CELLS

Walter Harrington1, Mwafaq R. Haji2, Alex Biris2, Ekaterina I. Galanzha1, Dmitry A. Nedosekin1, and Vladimir P. Zharov1

1Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.; 2Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, Arkansas, U.S.

The development of photoswitchable fluorescent proteins that can control light–dark states or spectral shifts in emission preferentially in UV and visible spectral range in response to light has led to breakthroughs in the tracking of individual biomolecules and cells. However, this approach is not applicable for use in deep tissue studies due to the strong auto-fluorescent background and toxicity concerns. We introduce a new concept of photoswitchable nanoparticles (NPs) that can undergo spectral shifts in absorption in near-infrared (NIR) range in response to light, which could be used in high sensitivity photoacoustic (PA) spectroscopy and imaging to track individual, non-fluorescence biomolecules and cells in deep tissue (up to a few cm). Here, we show the proof concept by designing a nanotechnology platform featuring tunable optical properties that has a potential for translation into clinics for detection, labeling and tracking of single cancer or bacterial cells. We demonstrate the feasibility of developing a photoswitchable system using sub-micrometer sized beads of thermochromic dye (TCD) coupled with iron oxide NPs to allow the optical control of dye properties. The high NIR absorbance of iron NPs permits the use of NIR laser light that is safe and minimally attenuated by live tissues. We demonstrate that changes in optical properties of TCD are reversible, fast and can be triggered remotely using laser light. These TCD beads can be incorporated into live cells. A single bead tracking technique based on PA microscopy method was developed and successfully implemented for identification of switchable bead absorption.

DISTINCT HOST IMMUNE RESPONSE TO GRAPHENE IN THE PRESENCE OR ABSENCE OF ENDOTOXIN

Kuppan Gokulan1, Mohamed Lahiani2, Katherine Williams1, Mariya V. Khodakovskaya2, and Sangeeta Khare1

1Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, U.S.; 2Department of Biology, University of Arkansas at Little Rock, Little Rock, Arkansas, U.S.

Synthesis and handing of nanomaterial can result in the end product being contaminated with endotoxin. The objective of this study was twofold. First, graphene-based nanomaterial was tested for the presence of endotoxin and the strategies were developed to reduce the level of endotoxin. Second, the study was conducted to distinguish the specific immune response exerted due to nanomaterial (graphene-based nanomaterial) versus the cumulative effect of nanomaterial and endotoxin.

Pristine graphene and functionalized graphene were used in this study. To detect endotoxin in the supplied material, the gel clot LAL assay and chromogenic-based LAL endotoxin system were used. Our results revealed that graphene contained significant amounts of endotoxin. Comparative analysis of various depyrogenic strategies was conducted. However, the concentration of endotoxin remains above FDA recommended limits at the graphene concentration >1ug/ml. Macrophages were incubated with depyrogenated and pristine graphene to test any differences in the phagocytosis of these material as well as gene expression of immune response related gene. Mechanism of uptake of depyrogenated graphene was different than the native graphene by macrophages. Both pristine and depyrogenated graphene caused down regulation of CD14 receptor on the macrophages; which may be due to the induction a signal transduction cascade involved in the binding of endotoxin on CD14.


Furthermore, there were several similarities as well as differences in the expression of Toll-like receptor signaling, NOD-like receptor signaling genes and downstream signal transduction molecule during the exposure of depyrogenated graphene. Most interestingly, depyrogenated graphene exposed macrophages dampened the expression of NF-kB signaling pathway. This study affirms the notion that endotoxin contamination should be assessed while evaluating the cellular toxicity to differentiate specific nanomaterial toxicity from the endotoxin effects.

DEVELOPMENT OF NOVEL ANALYTICAL TECHNIQUES FOR CHARACTERIZATION OF COMMERCIAL LIPOSOMES

Nuwan Kothalawala, Patrick Sisco, Andrew Fong, and Sean Linder

U.S. Food and Drug Administration, Office of Regulatory Affairs, Arkansas Regional Laboratory, Jefferson, Arkansas, U.S.

As the commercialization of liposomes has increased, regulatory-based methodologies for their physicochemical characterization have not been well documented. However, in an effort to ensure the safety and quality of commercialized liposomes, the development of methods for the characterization of their physical and chemical properties is imperative. Previously our laboratory has addressed some of these concerns by investigating methods for the characterization of particle size, size distribution, surface charge, shape and lamellarity. In this work, we have focused on both expanding the number of techniques available for the physical characterization of liposomes and the precise identification of the liposome’s chemical components using newly developed analytical methodologies. The physical characterization techniques include Resistive Pulse Sensing (RPS) with nanopores to determine particle size and size distribution. The chemical characterization techniques include hyphenated liquid chromatography (LC) with an evaporative light scattering detector (ELSD) or a charged aerosol detector (CAD) for lipid screening and separation followed by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Using these techniques along with lipid structure databases, such as LIPID MAPS and SIMLIPID, we can identify many of the commonly used lipids in commercially available liposomal drug formulations. This study allows for the development of an internal screening database for the identification of lipids present, as well as, the verification of the proper lipid ratios in a drug sample. The development of these advanced characterization methods will enable ORA to begin to address future regulatory issues related to commercial liposomal products.

TUNING THE SHAPE AND PROPERTIES OF MAGNETIC-OPTICAL CORE-SHELL NANOPARTICLES

Allie Elyahb Kwizera, Saheel Bhana, and Xiaohua Huang

Department of Chemistry, The University of Memphis, Memphis, Tennessee, U.S.

In the fight against cancer, half of the battle is won based on its early detection. Nanotechnology-based therapeutics have exhibited clear benefits when compared with unmodified drugs, including improved half-lives, retention, detecting and targeting efficiency, and fewer patient side effects. A major interest has been in the development of nanoparticles that combine multiple functions or properties that are not obtainable in individual materials. Some of those nanoparticles combine an optical signature originating from a gold shell layer with other physical properties, such as magnetisms which originates from the magnetic core. This combined property is particularly intriguing due to its applications in biomedicine, such as use in bio-separation or as magnetic resonance imaging. Our research goal is to develop novel magnetic and plasmonic hybrid nanoparticles with other related technology for cancer detection and treatment. We have developed a facile approach to prepare iron oxide-gold


core-shell nanostructures in different sizes and shapes, such as spheres, popcorns and stars, with integrated optical and magnetic properties. Different sizes and shapes were prepared by adjusting the amount of gold seed-adsorbed iron oxide nanoparticles and the amount of silver nitrate additives and reducing agents. By changing their shapes from sphere to star, significant red shift of the localized surface plasmon resonance peak was observed, with nanospheres at 570 nm, nanopopcorns at 650 nm and nanostars at 760 nm. The magnetic properties were confirmed by magnetization-field measurement and magnetic separation. The core-shell structures were confirmed by the presences of both iron and gold peaks in the energy-dispersive X-ray spectroscopy. These nanoparticles may offer next generation diagnostic and therapeutic products.

CARBON NANOMATERIALS AS TOOL FOR PLANT IMPROVEMENT

Mohamed H. Lahiani1, Jihua Chen2, Fahmida Irin3, Alexander A. Puretzky2, Micah J. Green3, and Mariya V. Khodakovskaya1

1Department of Applied Science, University of Arkansas at Little Rock, Little Rock, Arkansas, U.S.; 2Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee, U.S.; 3Department of Chemical Engineering, Texas Tech University, Lubbock, Texas, U.S.

Carbon-based nanomaterials can regulate seed germination and growth of plants developed for bio-energy, agriculture, medicine and other industrial applications (Khodakovskaya et al., 2011; Lahiani et al., 2013). We demonstrated that recently synthesized Single-Walled Carbon Nanohorns (SWCNHs) can interact with plants in a positive way and stimulate germination and plant growth as was previously seen for carbon nanotubes. Transmission electron microscopy (TEM) and microwave-induced heating (MIH) technique allowed us to detect and evaluate the uptake of SWCNHs by different crop species. Total transcriptome analysis (Affymetrix platform) of SWCNH-treated tomato plants reveled that SWCNHs can affect multiple genes involved in stress signaling, cellular responses and metabolic pathways. Our results proved potential of SWCNHs as plant growth regulators and suggested that Carbon Nanohorns can be used for delivery of different molecules to plant organs.

APPLICATION OF AVIAN IN VITRO AND IN VIVO MODELS TO MEASURE THE IMMUNOSTIMULATORY ACTIVITY OF INP/ZNS QUANTUM DOT NANOPARTICLES

Christopher S. Lyle1, Kristen A. Byrne1, Daniel M. Falcon1, Robert L. Dienglewicz1, Hyeonmin Jang1, Zoraida P. Aguilar2, and Gisela F. Erf1

1Department of Poultry Science, University of Arkansas, Fayetteville, Arkansas, U.S.; 2Zystein, LLC, Springdale, Arkansas, U.S.

Inorganic quantum dot nanoparticles have shown increasing promise in biological applications including enhanced immunostimulatory effects that may be leveraged as vaccine adjuvants. However, there remains a great need for effective in vitro and in vivo systems to measure toxicity and bioactivity of nanoparticles. The objective of this study was to utilize cultured chicken macrophages and antigen-injected growing feathers (GF) as in vitro and in vivo models, respectively, to examine the toxicity and bioactivity of 7 nm InP/ZnS quantum dots (QDs). In vitro studies revealed uptake of QDs within 45 minutes with minimal nitric oxide production and cytotoxicity. Using GF as a dermal test-site, innate cellular/tissue responses to different doses of QDs were examined over 7 days. To examine the primary and memory adaptive antibody response to test-antigen (mouse IgG; T-Ag), chickens were immunized (i.m.) with T-Ag, T-Ag mixed with Alum-adjuvant, or T-Ag conjugated QDs. For each response, blood was sampled before and 3, 5, 7, 10, 14, 21 and 28 days post-i.m. primary and secondary immunization. To determine the cellular immune response to T-Ag, GF were injected with T-Ag at the height of the primary/memory response and leukocyte infiltration into the pulp examined over 7 days.


Preliminary results indicate dose-dependent differences in innate responses to QDs injected into the dermis of GF and temporal, qualitative and quantitative differences in the humoral and cellular adaptive immune responses to T-Ag administered alone, mixed with Alum or conjugated to QDs. These data support our hypothesis that the avian system offers a unique opportunity to assess toxicity and bioactivity of nanoparticles for use in biological applications.

EFFECT OF GOLD NANOPARTICLES (AUNPS) ON AIRWAY SMOOTH MUSCLE TONE

Daniel Alberto Maldonado Ortega, Deyanira B. López Dimas, Manuel Alejandro Ramírez Lee, and Carmen Gonzalez

Universidad Autonoma de San Luis Potosi, Facultad de Ciencias Quimicas, San Luis Potosi, Mexico

AuNPs have been used in biomedical and therapeutic tools against cancer, imaging and targeted drug delivery. However, their role in the respiratory physiology has been poorly studied. The aim of this study was to evaluate the effect of AuNPs (15 ± 3 nm) on airway smooth muscle (ASM) tone, using isolated rat tracheal rings, pre-contracted tracheal rings with acetylcholine (ACh), a very well-known contractile agent. The results obtained showed that AuNPs did not modify the ASM tone in a concentration range of 0.1-10 µg/mL, suggesting that these NPs could be considered as bio-inert at these doses. On the other hand, concentrations equal to or greater than 100 µg/mL of AuNPs exerted a contractile effect evidenced by the increased tension of the ring, which could be related with hyper-reactivity, a pathological event observed in airway inflammatory diseases, such as asthma. Preliminary data indicate that the observed physiological effects were found to be related with the production of nitric oxide (NO), which was quantified by Griess method. Considering that NO has concentration-dependent dual effects on smooth muscle, our results suggest that this free radical could be a mediator involved in the effects induced by AuNPs on ASM tone. However, further investigations must be performed to establish a range of biosafety that has a great biological impact, since this property will support the development, innovation and study of targeted drug delivery at specific regions of the airway.

GENOTOXICITY OF NANOMATERIALS: REFINING STRATEGIES AND TESTS FOR HAZARD IDENTIFICATION

Mugimane G. Manjanatha1, Stefan Pfuhler2, Rosalie Elespuru3, Marilyn J. Aardema4, Shareen H. Doak5, E. Maria Donner6, Masamitsu Honma7, Micheline Kirsch-Volders8, Robert Landsiedel9, Tim Singer10, and James H. Kim11

1U.S. Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, U.S.; 2Procter and Gamble Co., Miami Valley Innovation Center, Cincinnati, Ohio, U.S.; 3U.S. Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, Maryland, U.S.; 4Marilyn Aardema Consulting LLC, Fairfield, Ohio, U.S.; 5College of Medicine, Swansea University, Singleton Park, Swansea, Wales, United Kingdom; 6DuPont Haskell Global Centers for Health & Environmental Sciences, Newark, Delaware, U.S.; 7National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan; 8Vrije Universiteit Brussel, Belgium; 9BASF SE, Ludwigshafen, Germany; 10Health Canada, Ottawa, Ontario, Canada; 11Executive Office of the President, Clarksville, Maryland, U.S.

A workshop addressing strategies for the genotoxicity assessment of nanomaterials (NMs) was organized by the Environmental Mutagen Society and the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute. The workshop was attended by more than 80 participants from academia, regulatory agencies and industry from North America, Europe and Japan. A plenary session featured summaries of the current status and issues related to the testing of NMs for genotoxic properties, as well as an update on international activities and regulatory approaches. This was followed by breakout sessions and a plenary session devoted to independent discussions of in vitro assays, in vivo assays and the need for new assays or new approaches to develop a testing strategy for NMs. Each of the standard


assays was critiqued as a resource for evaluation of NMs, and it became apparent that none was appropriate without special considerations or modifications. The need for nano-specific positive controls was questioned, as was the utility of bacterial (Ames) assays. The latter was thought to increase the importance of including mammalian cell gene mutation assays into the test battery. For in-vivo testing, to inform the selection of appropriate tests or protocols, it was suggested to run repeated dose studies first to learn about disposition, potential accumulation and possible tissue damage. It was acknowledged that mechanisms may be at play that a standard genotoxicity battery may not be able to capture. The report of this workshop was published in 2013 and the report will be presented in this poster.

BIOINSPIRED MELANIN NANOSTRUCTURES AS HIGH CONTRAST PHOTOACOUSTIC AGENTS FOR BIOMEDICAL APPLICATION

Yulian A. Menyaev, Kai Carey, Jacqueline Nolan, Mustafa Sarimollaoglu, Dmitry A. Nedosekin, Ekaterina I. Galanzha, and Vladimir P. Zharov


Unprecedented advances in nanotechnology promise to revolutionize cancer diagnosis and therapy. Nevertheless, challenges still remain in treating cancer metastasis—a leading cause of death in the U.S. and worldwide. Many studies have demonstrated the potential of circulating tumor cells (CTCs) as prognostic markers; however incurable metastases are often established at the time of initial diagnosis with existing low sensitivity CTC assays. In addition, the use of artificial nanoparticles (NPs), in particular plasmonic NPs for detection of CTCs in humans, especially in vivo is still challenging due to toxicity concerns, unpredictable NP aggregation and the problem with specific molecular targeting. We have recently demonstrated dramatic (102-fold) improvement in the detection of pigmented CTCs in vivo in melanoma patients using natural melanin NPs as intrinsic photoacoustic (PA) contrast agents. Nevertheless, the properties of these unique NPs are not yet well characterized. Here, based on the literature and our own research with melanoma cell lines (e.g., B16F10 and HTB65), melanin from various organism and melanosomes we present comprehensive evaluation of melanin nanostructure parameters with focus on natural melanin synthesis, its enhancement by radiation and drugs, genetic engineering of melanin NPs in non-pigmented live cells using a plasmid expressing tyrosinase gene, optical and PA spectral melanin contrast and NP shape and size distribution. We demonstrate spectrally selective detection of both melanoma CTCs and melanoma-associated exosomes, which has potential to dramatically improve melanoma diagnosis. Our results show that melanin nanostructures could serve as universal PA reporters in analogy to green fluorescent protein in fluorescence techniques.

SURFACE ENHANCED RAMAN SPECTROSCOPY (SERS) BASED RAPID MULTICOMPONENT SCREENING METHOD FOR IDENTIFICATION OF THREE ILLEGAL ANTIMICROBIAL AGENTS IN AQUATIC FOOD

Yasith S. Nanayakkara1,2, Sean W. Linder1, and Andrew Fong1

1Office of Regulatory Affairs, U.S. Food and Drug Administration, Jefferson, Arkansas, U.S.; 2Office of the Commissioner, U.S. Food and Drug Administration, Silver Spring, Maryland, U.S.

Surface Enhanced Raman Spectroscopy (SERS) is a powerful analytical technique, which uses silver or gold nanomaterial substrates. These nanomaterials generate surface plasmon resonances and can enhance the inherent Raman signal by several orders of magnitude. For this project we investigated three illegal antimicrobial agents with closely related structures (say A, B and C) that have been found in imported aquatic food. The aquatic food (shrimp) samples were spiked with antimicrobial agents to obtain sample combinations of A, B, C, AB,


AC, BC and ABC (10 ng/g each component). The samples were then treated with hydroxylamine, magnesium sulfate and alumina respectively and extracted with acetonitrile (total extraction process ~ 20 minutes per sample). 20 µL of the extract was pipetted onto a gold SERS substrate. Finally it was analyzed with a HORIBA LabRAMHR Raman spectrophotometer. The obtained unique spectra were analyzed using principal component analysis and classical least squares techniques. Both models were capable of identifying the antimicrobial agents in each sample. The antimicrobial positive samples can be further confirmed by LC-MS/MS (LC-liquid chromatography, MS-mass spectroscopy), which is more time/labor consuming (~ 10 hours). The results confirm that SERS can be used for rapid screening of illegal antimicrobial agents in seafood providing a way to minimize number of samples needed to be analyzed by LC-MS/MS. Raman spectrometers cost an order of magnitude less than an LC-MS/MS. Since portable/handheld Raman spectrometers are commercially available, this has the potential to be adapted for field use. Hence this method is economical to the FDA.

DETECTION OF NANOPARTICLE- AND DRUG-INDUCED APOPTOSIS IN CIRCULATING CELLS IN VIVO

Jacqueline Nolan, Chenzhoung Cai, Dmitry A. Nedosekin, and Vladimir P. Zharov


The detection and enumeration of apoptotic and necrotic cells in response to nanoparticles (NPs) is important to control nanoparticle toxicity and efficiency of anti-tumor therapy. Previous studies recorded in vitro are not able to be effectively translated into in vivo conditions, as invasive extraction of cells from a living system may alter cell properties (e.g., morphology or marker expression), induce artifacts or prevent the long-term study of cell-NP and cell-drug interactions in their biological environment. Another limitation is the low sensitivity in detecting rare circulating apoptotic tumor cells (CTCs) that are indicators of metastatic progression. Here we show that these limitations can be overcome by the use of in vivo flow cytometry (FC), which allows real-time monitoring of circulating normal blood cells and CTCs in response to NPs and anti-tumor drugs. We introduce high speed, multicolor in vivo FC that integrates photoacoustic (PA) fluorescence FC (PAFFC) to demonstrate a promising preliminary application of this unique technique for detection of rare circulating apoptotic cells in a mouse model. The verification of this approach was performed initially in vitro by the induction of apoptosis in cancer cells using a chemical apoptotic inductor (H2O2) and compared with apoptosis induced by graphene NPs followed by the injection of these cells in the circulatory system of a mouse. PA and fluorescence channels were used to detect cells with graphene and apoptotic cells in micro-vessels of the mouse’s ear. The coincidence of PA and fluorescence signals indicated cells with graphene–induced apoptosis.

MULTIPLEXED TARGETING, ISOLATION AND CHARACTERIZATION OF TUMOR CELLS IN BLOOD WITH IRON OXIDE-GOLD CORE-SHELL NANOSTARS

Ryan O’Connor, Allie Elyahb, Saheel Bhana, and Xiaohua Huang

Department of Chemistry, The University of Memphis, Memphis, Tennessee, U.S.

Metastasis accounts for 90% of cancer deaths. Metastasis is established by shedding tumor cells into blood, which then travel to distinct organs and initiate new tumors. Thus, detection of tumor cells in blood can detect metastasis at an early stage and monitor tumor progression. However, detection of these cells is very difficult because they are rare cells and heterogeneous populations. A general strategy to address these challenges is to combine isolation and detection technologies. Especially, multiplexed targeting is very important


to address the heterogeneous problems. We report the use of iron oxide-gold core-shell nanostars for Raman-based multiplexed targeting, isolation and detection of tumor cells in blood. We systematically examined the specificity and affinity of 4 color iron oxide-gold core-shell nanostars targeting four different markers: epithelial cell adhesion molecule, human epidermal growth factor receptor 2, epidermal growth factor receptor and insulin growth factor 1 receptor. We also tested the capability of the multiplexed nanostars to simultaneously isolate spiked breast cancer cells with these markers in human whole blood based on magnetic separation and to detect these multi-population cancer cells at single cell level with a portable Raman microscope. Preliminary results show that this simple assay can lead to more than 95% tumor cell capture efficiency and recovery. Quantitative information on the marker expression on single cells was also achieved based on the surface enhanced Raman scattering signals from the reporters coated on the dually functional nanoparticles.

SINGLE-WALLED CARBON NANOTUBES (SWCNTS) INDUCE VASODILATION IN ISOLATED RAT AORTIC RINGS

Manuel Alejandro Ramirez-Lee2, José Manuel Gutiérrez-Hernández1, Hector Rosas-Hernandez2, Samuel Salazar-García2, Daniel Alberto Maldonado-Ortega2, Francisco J. González1, Syed F. Ali3, Carmen Gonzalez2

1Universidad Autonoma de San Luis Potosi, Coordinacion para la Innovacion y la Aplicacion de la Ciencia y la Tecnologia, San Luis Potosi, Mexico; 2Universidad Autonoma de San Luis Potosi, Facultad de Ciencias Quimicas, San Luis Potosi, Mexico; 3Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, U.S..

Single-walled carbon nanotubes (SWCNTs) are used in biological systems with impact in biomedicine in order to improve diagnostics and treatment of diseases. However, their effects upon the vascular system are not fully understood. Endothelium and smooth muscle cells (SMC) communicate through the release of vasoactive factors, such as nitric oxide (NO), to maintain vascular tone. The aim of this study was to evaluate the effect of SWCNTs on vascular tone using an isolated rat aortic rings model. Aortic rings were exposed to SWCNTs (0.1, 1 and 10 μg/mL) both in presence and absence of endothelium. SWCNTs induced vasodilation in both conditions, indicating that this effect was not dependent on endothelium presence, and moreover that vasodilation was independent on NO production, since its blockage with L-NG-Nitroarginine methyl ester (L-NAME) did not modify the observed effect. Together, these results indicate that SWCNTs induce vasodilation in the macrovasculature, may be through a direct interaction with SMC rather than endothelium without involving the NO production. Further investigation is required to fully understand the mechanisms of action and mediators involved in the signaling pathway induced by SWCNTs on the vascular system components under specific biological conditions.

COMPARATIVE EFFECTS ON RAT PRIMARY ASTROCYTES AND C6 RAT GLIOMA CELLS CULTURES AFTER 24 HOURS EXPOSURE TO SILVER NANOPARTICLES (AGNPS)

Samuel Salazar-García1, Ana Sonia Silva-Ramírez1, Manuel A. Ramirez-Lee1, Hector Rosas-Hernandez1, Edgar Rangel-López2, Claudia G. Castillo3, Abel Santamaría2, Gabriel A. Martinez-Castañon4, and Carmen Gonzalez1

1Universidad Autónoma de San Luis Potosí, Facultad de Ciencias Químicas, San Luis Potosi, Mexico; 2Laboratorio de Aminoacidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, Mexico; 3Universidad Autonoma de San Luis Potosi, Facultad de Medicina, San Luis Potosi, Mexico; 4Universidad Autonoma de San Luis Potosi, Facultad de Estomatologia, San Luis Potosi, Mexico

The aim of this work was to compare the effects of 24 hours exposure of rat primary astrocytes and C6 rat glioma cells to 7.8 nm AgNPs. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and current treatments lead to diverse side effects; for this reason, it is imperative to investigate new approaches, including those alternatives provided by


nanotechnology, like such nanomaterials (NMs) as silver nanoparticles. Herein, we found that C6 rat glioma cells, but no primary astrocytes, decreased cell viability after AgNPs treatment; however, both cell types diminished their proliferation. The decrease of glioma C6 cells proliferation was related with necrosis, while in primary astrocytes the decreased proliferation was associated with the induction of apoptosis. The ionic control (AgNO3) exerted a different profile than AgNPs; the bulk form did not modify the basal effect in each determination whereas cisplatin, a well-known antitumoral drug used as a comparative control, promoted cytotoxicity in both cell types at specific concentrations. Our findings prompt the need to determine the fine molecular and cellular mechanisms involved in the differential biological responses of AgNPs in order to develop new tools or alternatives based on nanotechnology that may contribute to the understanding, impact and use of NMs in specific targets, like glioblastoma cells.

ANALYTICAL METHODOLOGIES TO ISOLATE AND QUANTIFY FREE AND LIPOSOMAL BOUND DOXORUBICIN FROM BIOLOGICAL SAMPLES USING LC-MS

Patrick Sisco1, Nuwan Kothalawala1, Nathan Koonce2, Kristen Ahlschwede2, Julian Leakey2, Andrew Fong1, and Sean Linder1

1U.S. Food and Drug Administration, Office of Regulatory Affairs, Jefferson, Arkansas, U.S.; 2U.S. Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas, U.S.

As the commercialization of liposomes has increased, regulatory-based analytical methodologies to investigate nanoparticle biodistribution have not been well documented. As such, to ensure the safety and quality of liposomal products, the development of analytical methodologies to quantitatively describe nanoparticle biodistribution is essential. In this work, we have focused on the development of analytical methods, rooted in the use of liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS), triple quadrupole mass spectrometry (QQQ-MS) and quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) to isolate and quantify doxorubicin from tissues and plasma samples. The first method was developed to isolate and quantify both free doxorubicin and liposomal bound doxorubicin in blood plasma. We based this separation upon the selective retention of free doxorubicin on a hydrophobic reversed-phase solid phase extraction (SPE) cartridge. The liposomal fraction exhibited no retention, while the free doxorubicin was retained on the column and eluted with acidified methanol. The liposomal fraction was collected, treated with acetonitrile to extract the doxorubicin and isolated using SPE. After extraction the samples were run on LC-QQQ-MS or LC-Q-TOF-MS to quantify the amount of doxorubicin present in each fraction. The second method was developed to extract and quantify total doxorubicin from tissues. In this method we extract the doxorubicin from homogenized tissue made by disrupting biological samples through high-speed shaking in plastic tubes with stainless steel beads. The total doxorubicin is quantified using LC-HRMS. The development of these advanced analytical methods will enable FDA to begin to address future regulatory issues related to liposomal drug products.


DESIGNATION OF VIABILITY OF HEPATITIS A ASSAY ELUATE VIA QUARTZ CRYSTAL MICROBALANCE

Stephen Torosian1, Aaron Bandremer1, Hilal Goktas1,2, and Tanmay Bera3

1U.S. Food and Drug Administration, Winchester Engineering and Analytical Center, Winchester, Massachusetts, U.S.; 2Massachusetts Institute of Technology, Chemical Engineering Department, Cambridge, Massachusetts, U.S.; 3U.S. Food and Drug Administration, Arkansas Regional Lab, Jefferson, Arkansas, U.S.

Quartz Crystal Microbalance (QCM) is a label-free and an emerging tool in biological research for rapid diagnosis of virus. We are investigating the ability of QCM technique to rapidly assess the viability of the non-pathogenic HAV virusHM175 from eluate(s) of the BAM HAV method. The quartz crystals employed in QCM have a piezoelectric character, which allows measurement of nano gram changes in mass that occur on the surface of the crystals. Researchers have used QCM to specifically trap viruses, but QCM has not been used to verify the growth of viral numbers within a live cell or cell population. We are employing QCM to measure frequency changes in minutes when a cell line, Fetal Rhesus Kidney (frhk) cells are inoculated with viral assay extract spiked with HAV. Frequency measurement changes of a spiked sample can be compared to frequency measurements from frhk cells that have not been spiked with HAV. When mass changes of the spiked sample versus the unspiked sample occur, viral growth (viability) is occurring. This tool may be adaptable to quickly verify the potential infectivity of a regulatory viral assay isolate. Ongoing efforts are exploring additional species of viral viability targets.

POLYETHYLENE GLYCOL-FUNCTIONALIZED POLY(LACTIDE-CO-GLYCOLIDE) AND GRAPHENE OXIDE NANOPARTICLES INDUCE PRO-INFLAMMATORY AND CELL STRESS RESPONSES IN CULTURED VAGINAL EPITHELIAL CELLS INFECTED WITH CANDIDA ALBICANS

R. Doug Wagner, Ph.D.1; Shemedia J. Johnson1, Sean Linder2, and Zhixia Yan3

1National Center for Toxicological Research, Microbiology Division, Jefferson, Arkansas, U.S.; 2Arkansas Regional Laboratory of the U.S. Food and Drug Administration, Jefferson, Arkansas, U.S.; 3Center for Drug Evaluation and Research, Office of Pharmacology, U.S. Food and Drug Administration, White Oak, Maryland, U.S.

Mucous-penetrating nanoparticles consisting of poly lactide-co-glycolide (PLGA)-polyethylene glycol (PEG) or graphene oxide-PEG could improve targeting of microbicidal drugs for sexually transmitted diseases by intravaginal inoculation. Nanoparticles may induce inflammatory responses, which may exacerbate the inflammation that occurs in the vaginal tracts of women with yeast infections. Vaginal epithelial cell monolayers infected with C. albicans were exposed to 100 µg/ml 116 nm PLGA-PEG nanospheres or 1 nm thick GO-PEG sheets and assessed for changes in expression of proinflammatory-related genes by qRT-PCR and physiological markers of cell stress by high content analysis and flow cytometry. C. albicans exposure suppressed apoptotic gene expression but induced oxidative stress and pyroptosis (NLRP3 expression, IL-18 excretion, and CASP1 activation) in the cells. The nanomaterials induced cytotoxicity (LDH release) and programmed cell death responses alone and with C. albicans. PLGA-PEG nanoparticles induced expression of apoptosis and pyroptosis-related genes (BID, BNIP3, CASP 1, 3, 7, TNF, NOD2) and induced PARP cleavage, chromatin condensation, increased BAX/BCL2 ratio and Annexin V binding. They also induced autophagy, endoplasmic reticulum stress (aggregesome formation), DNA damage (γH2AX accumulation) and lipid peroxidation. They caused the cells to excrete inflammatory recruitment molecules CXCL1, IL1A, IL1B, S100A8 and TNF. GO-PEG nanoparticles induced mRNA expression of necrosis-related genes (NOD2, NLRP6, DRAM2, BID, DEFB1, CXCL8, TNF) and LDH release. They reduced autophagosome and aggregesome production, and apoptotic responses, thus, causing cytotoxicity by a different mechanism. The results show that stealth nanoparticle drug-


delivery vehicles cause intracellular damage by several mechanisms and suggest their use for intravaginal drug delivery may exacerbate inflammation in active yeast infections.

DETECTION OF BOTULINUM NEUROTOXIN USING FRET-BASED QUANTUM DOT SENSOR

Yun Wang1, Timothy V. Duncan1, Kristin M. Schill1, Guy E. Skinner1, H. Christopher Fry2, and Igor L. Medintz3

1Division of Food Processing Science and Technology, U.S. Food and Drug Administration, Bedford Park, Illinois, U.S.; 2Center for Nanoscale Materials, Argonne National Laboratory, Lemont, Illinois, U.S.; 3Center for Bio/Molecular Science and Engineering, U.S. Naval Research Laboratory, Washington, D.C., U.S.

Foodborne botulism results from oral ingestion of botulinum neurotoxin (BoNT), which is the most potent toxin known to humans. Currently, the gold standard method of BoNT detection is the mouse bioassay, which is time consuming, expensive and poses ethical concerns over the use of laboratory animals. Herein, we report the detection of biologically active botulinum neurotoxin A (BoNT/A) using quantum dots (QDs) functionalized with intelligently designed peptides as probes. Fluorescence quenchers (FQs) were tethered to QDs through the linkage of peptides that contain cleavage sites that are specific for BoNT/A, and this quenching effect maintains a “dark” state of QDs. In the presence of biologically active BoNT/A, the peptides were cleaved and the quenching of QD fluorescence was removed, resulting in a “turning on” of the QDs from the “dark” state. Therefore, the assay is only sensitive to biologically active toxins. Mass spectrometry showed the cleavage of the peptides by BoNT/A light chain, which is the catalytic domain of the toxin. The quenching effect was observed and the decrease in QD fluorescence directly related to the amount of the peptide attached to the QDs (peptide-FQ: QD). Factors, such as the presence of reductants, shelf-life of the probe and buffers, were found to affect the performance of the detection system. BoNT/A light chain at the concentration of 40~160 nM and BoNT/A holotoxin were detected using the sensor. This sensor can detect BoNT without the need of expensive instrumentation or lengthy incubation times.

EFFECTS OF SILVER NANOPARTICLE EXPOSURE ON INTESTINAL PERMEABILITY IN AN IN VITRO MODEL OF THE HUMAN GUT EPITHELIUM

Katherine Williams, Kuppan Gokulan, Carl E. Cerniglia, and Sangeeta Khare

Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, U.S.

The antimicrobial activity of silver nanoparticles (AgNP) has led to their increasing incorporation into household goods, such as food utensils and storage containers, suggesting that consumer use of these products could result in gastrointestinal exposure. The health impact of AgNP exposure is unknown, especially effects related to intestinal permeability and barrier function. This study examined the effects of AgNP exposure of different sizes (10 nm, 20 nm, 75 nm and 110 nm) and doses (20 µg/mL and 100 µg/mL) on the permeability of an in vitro model of the human gut epithelium. Results showed that effects of AgNP on the T84 human colonic epithelial cells were size- and dose-dependent, with the 10 nm AgNP causing the most significant changes. Changes in permeability of the epithelial cell monolayer, as measured by transepithelial resistance (TER), after exposure to 10 nm AgNP were most dramatic at the highest dose (100 µg/mL), but also observed at the lower dose (20 µg/mL). AgNP could be visualized inside cells using transmission electron microscopy (TEM) and silver was detected in basal wells using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Exposure to AgNP significantly affected the expression of genes involved in anchoring tight junctions, cellular proliferation and signaling, endocytosis and cell-cell adhesion, with the 10 nm AgNP having the greatest effect. The results of this study show that small-size AgNP have significant


effects on intestinal permeability in an in vitro model of the human gastrointestinal epithelium. Such effects could potentially compromise the integrity of the epithelial cell barrier and this disruption might lead to health risks.


THURSDAY, DECEMBER 3, 2015ABSTRACTS


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POLYMERIC NANOPARTICLES FOR ORAL DELIVERY OF DRUGS: EFFICACY AND SAFETY ASSESSMENT

Cristina Sabliov

Louisiana State University, Baton Rouge, Louisiana, U.S.

Poor drug stability, low water solubility and limited bioavailability are some of the challenges encountered in oral drug delivery. It is generally accepted that polymeric nanoparticles offer distinct advantages over traditional methods for delivery of bioactives, such as improved stability, controlled release kinetics and targeting of the bioactive for enhanced uptake and functionality of the bioactive. While the advantages of nanodelivery systems for health applications are supported by a wealth of data, the interaction of nanoparticles with the human body is complex and not fully understood, especially for orally delivered, organic nanoparticles. Due to their small size, nanoparticles have the potential to translocate to various parts of the body, raising concerns about their safety. Safety profiles are specific to the type of delivery system and associated properties, and toxicity assessment is hence a challenging and expensive task for researchers and regulatory agencies. The effect of nanoparticle properties on the functionality of the entrapped bioactive and on the biodistribution and safety of the nanoparticles will be covered in this presentation. This multifaceted understanding of nanoparticle behavior in vivo and its effect on the drug biodistribution, efficacy and safety is absolutely critical for rapid development of safe nanodelivery systems for health applications.

PLENARY ABSTRACTS


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POLYMERIC NANOPARTICLES FOR ORAL DELIVERY OF DRUGS: EFFICACY AND SAFETY ASSESSMENT


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NANOGENERATORS FOR SELF-POWERED SYSTEMS AND PIEZOTRONICS FOR SMART DEVICES

Zhong Lin Wang

School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia, U.S.

Developing wireless nanodevices and nanosystems is of critical importance for sensing, medical science, environmental/infrastructure monitoring, defense technology and even personal electronics. It is highly desirable for wireless devices to be self-powered without using a battery. Nanogenerators (NGs) have been developed based on piezoelectric, trioboelectric and pyroelectric effects, aiming at building self-sufficient power sources for mico/nano-systems. The output of the nanogenerators now is high enough to drive a wireless sensor system and charge a battery for a cellphone, and they are becoming a vital technology for sustainable, independent and maintenance-free operation of micro/nano-systems and mobile/portable electronics. An energy conversion efficiency of 55% and an output power density of 500 W/m2 have been demonstrated. This technology is now not only capable of driving portable electronics, but also has the potential for harvesting wind and ocean wave energy for large-scale power application. This talk will focus on the updated progress in NGs.

For Wurtzite and zinc blend structures that have non-central symmetry, such as ZnO, GaN and InN, a piezoelectric potential (piezopotential) is created in the crystal by applying a strain. Such piezopotential can serve as a “gate” voltage that can effectively tune/control the charge transport across an interface/junction; electronics fabricated based on such a mechanism is coined as piezotronics, with applications in force/pressure triggered/controlled electronic devices, sensors, logic units and memory. By using the piezotronic effect, we show that the optoelectronc devices fabricated using wurtzite materials can have superior performance as solar cell, photon detector and light emitting diode. Piezotronics is likely to serve as a “mechanosensation” for directly interfacing biomechanical action with silicon based technology and active flexible electronics. This lecture will focus on the updated progress in the field and its expansion to 2D materials.References

[1] G. Zhu, J. Chen, T.J. Zhang, Q.S. Jing, Z.L. Wang “Radial-arrayed rotary electrification for high-performance triboelectric generator”, Nature Communication, 5 (2014) 3456.[2] W.Z. Wu+, X.N. Wen+, Z.L. Wang “Pixel-addressable matrix of vertical-nanowire piezotronic transistors for active/adaptive tactile imaging”, Science, 340 (2013) 952-957.[3] C.F. Pan, L. Dong, G. Zhu, S. Niu, R. Yu, Q. Yang, Y. Liu, Z.L. Wang “Micrometer-resolution electroluminescence parallel-imaging of pressure distribution using piezoelectric nanowire-LED array”, Nature Photonics, 7 (2013) 752-758.[4] W.Z. Wu, L. Wang, Y.L. Li, F. Zhang, L. Lin, S. Niu, D. Chenet, X. Zhang, Y. Hao, T.F. Heinz, J. Hone, and Z.L. Wang “Piezoelectricity of single-atomic-layer MoS2 for energy conversion and piezotronics”, Nature, 514 (2014) 470-474.


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NANOGENERATORS FOR SELF-POWERED SYSTEMS AND PIEZOTRONICS FOR SMART DEVICES


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ENGINEERED METALLIC NANOPARTICLES: PRO-INFLAMMATORY RESPONSE AND EFFECTS ON INTEGRITY OF BLOOD-BRAIN BARRIER

Syed Ali1, Susan Lantz-McPeak1, Bonnie Robinson1, Hector Rosas-Hernandez1,2, Carmen Gonzalez2, William Trickler1, Saber Hussain3, and Alexandru Biris4

1Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, U.S.; 2Universidad Autonoma de San Luis Potosi, Coordinacion para la Innovacion y la Aplicacion de la Ciencia y la Tecnologia, San Luis Potosi, Mexico; 3Applied Biotechnology Branch, Human Effectiveness Directorate, Air Force Research Laboratory, Wright-Patterson Air Force Base, Ohio, U.S.; 4Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, Arkansas, U.S.

The purpose of the current studies was to determine what role the microvessel endothelial cells play in brain inflammation and neurotoxicity associated with colloidal metallic nanoparticles (NPs). A primary culture of rat brain microvessel endothelial cells (rMVEC) was isolated by enzymatic digestions and differential centrifugation for an in vitro model of the BBB. Confluent rMVEC monolayers were treated with various sized Ag, Au or Cu NPs. The cellular accumulation of the NPs was determined spectrophotometrically at various time intervals. The cytotoxicity was evaluated by XTT in rMVEC following 24 hours of NPs exposure. The extracellular concentrations of pro-inflammatory mediators were evaluated by ELISA at various time intervals (0, 2, 4, 6 and 8 hours) following exposure to various sized Ag, Au or Cu NPs. The magnitude of cellular accumulation was size dependent and similar for all NPs over the experimental period. The cytotoxicity of rMVEC following 24 hours of exposure to Ag-NPs and 10ug/ml (40 and 80 nm) was significantly increased, when compared to Au-NPs whereas Cu-NPs LD50 was approximately 12.5 ug/ml for both sized. Au-NPs above 3 nm in size showed no significant cytotoxic effects. PGE2 release following Ag and Cu NPs exposure was significantly increased when compared to control at the end of the 8-hour experiment. The basal levels of TNF and IL-1B were significantly increased following Ag or Cu NPs, but not with Au-NPs. These data suggest that the brain microvessel endothelial cells may play a significant role in the neurotoxicity associated with Ag, Au or Cu NPs.

WORKSHOP 3 – INTERACTIONS, IMPACT AND USE OF NANOMATERIALS FOR COMPLEX BIOLOGICAL SYSTEMS

WORKSHOP ABSTRACTS


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ENGINEERED METALLIC NANOPARTICLES: PRO-INFLAMMATORY RESPONSE AND EFFECTS ON INTEGRITY OF BLOOD-BRAIN BARRIER


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GRAPHENE-BASED NANOMATERIAL SCAFFOLDS FOR BONE TISSUE ENGINEERING

Madhu S. Dhar

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, U.S.

Current treatments for bone injuries involve autologous and allogenic bone grafts, metal alloys and ceramics. Even though these therapies have proved to be useful, they suffer from inherent challenges and, hence, an adequate bone replacement therapy is yet to be found. We propose to study graphene as a potential backbone for multi-component nanostructural biomimetic scaffolds designed to have a chemical and morphological structure similar to bone. We hypothesize that oxidized graphene can serve as a favorable 2- and 3-dimensional osteo-inducer and as a vehicle to deliver adult mesenchymal stem cells. To prove our hypothesis, the first step is to test the in vitro adherence, growth and differentiation of mesenchymal stem cells on this nanomaterial. Results of these tests will guide in vivo trials. Using the classical method of Ficoll centrifugation, adult mesenchymal stem cells were isolated from the bone marrow aspirate of a 2-year-old mixed breed goat. Cells were expanded ex vivo; and cell proliferation, live-dead staining and osteogenesis assays were performed in presence of both the polystyrene-coated and oxidized graphene-coated tissue culture plates. Graphene films were not toxic and supported cell adhesion and proliferation. Importantly, mesenchymal cells seeded on graphene films underwent osteogenic differentiation in the fetal bovine serum-containing medium without the addition of any glucocorticoid or growth factors. These findings support graphene’s potential to act as an osteo-inducer and a cell delivery vehicle. An optimal combination of a multicomponent nanoscale graphene-based nanomaterial and mesenchymal stem cells could form the foundation for novel scaffold technology to promote rapid bone regeneration with the goal of improving human health and rehabilitation.


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GRAPHENE-BASED NANOMATERIAL SCAFFOLDS FOR BONE TISSUE ENGINEERING


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NANOSCALE MATERIALS AND SENSORS IN CARDIOVASCULAR MEDICINE

Morten Jensen

University of Arkansas, Fayetteville, Arkansas, U.S.

The potential of enhancing and developing new concepts for treatment, diagnosis and prevention of cardiovascular disease with nanotechnology is limited by nothing but imagination.

The first part of this presentation will provide an overview of the current state-of-the-art technology in cardiovascular transducers. Current methods for measuring biomechanical fluid and tissue parameters are mostly based on sensing the deformation of a specific element. Nanotechnologies, such as carbon-nanotubes and micro-electro-mechanical systems (MEMS), can become an integrated part of the transducer, minimizing the footprint and optimizing the durability of and signal quality from the device. Several challenges remain to be addressed, such as supplying secure wires to and from these transducers or alternatively establish sufficient power-supply and signal transfer wirelessly.

The second part of the talk will discuss the direct application of nanotechnology in cardiovascular medicine. These translational endeavors present a number of challenges, which require direct and intensive collaboration between basic scientists, engineers and clinicians. One example that will be presented is the treatment of cardiac ischemia with nano-conjugated stem cells. For this direct clinical use, complete safety and biocompatibility profiles and long-term results are still pending and needed before nanotechnology can be fully utilized in cardiovascular medicine.

Success with nanotechnologies has a potential to result in a paradigm shift in the way we look at cardiovascular intervention and transducer design for tissue engineering. The time required to make solutions of the challenges will depend on the strength and efficiency of multidisciplinary collaborations.

WORKSHOP 4 – BIOSENSORS AND TRANSDUCERS FOR MEDICAL APPLICATIONS (NANOSCALE MATERIALS AND SENSORS IN CARDIOVASCULAR MEDICINE)


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NANOSCALE MATERIALS AND SENSORS IN CARDIOVASCULAR MEDICINE


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RECENT DISCOVERIES AND FUTURE NEEDS IN THE PREVENTION AND TREATMENT OF VISION LOSS

John P. Shock

University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.

The National Federation of the Blind considers individuals to have low vision if their sight is bad enough that they must use alternative methods to engage in any activity that persons with normal vision do using their eyes and/or corrective lenses. The statutory definition of “legally blind” is that central visual activity must be 20/200 or less in the better eye with the best possible correction, or that the visual field must be 20 degrees or less. In other words, they can barely see the big “E” on the chart. Although this covers the most severe vision loss, there are several million additional individuals in the U.S. who have permanent uncorrectable vision loss that require visual aids to function in our society. According to the 2012 National Health Interview Survey, 20.6 million American adults fall into this category that are age 18 years an older.

The two major causes of permanent vision loss are chronic open angle glaucoma (COAG) and age-related macular degeneration (ARMD). The primary treatment for both of these conditions is drugs suspended in liquids delivered either by drops on the cornea (COAG), or injection through the sclera into the vitreous cavity (ARMD).

Typically less than 5% of the medicine dose applied as drops actually penetrates the eye before they are washed away by the tears. At Ohio State University and the University of Reading they are working on a potential way of making drops more effective by developing novel nanoparticles that adhere to the cornea and when loaded with drugs would resist being washed away.

Wet macular degeneration (bleeding) has been treated for several years with anti-VEGF medications that slow the growth of abnormal blood vessels in the back of the eye where ARMD occurs. The Ohio State group is developing a more efficient drug delivery method for anti-VEGF medication using microsonic particles known as nanobubbles. The strategy is to selectively activate these bubbles using ultrasound when they reach the targeted area thus making the injection more efficient.


Notes

RECENT DISCOVERIES AND FUTURE NEEDS IN THE PREVENTION AND TREATMENT OF VISION LOSS


Notes

Gregory Farber, Ph.D.1; Carlos Pena, Ph.D.2; Justin Sanchez, Ph.D.3; and Amber Story, Ph.D.4

1NIH, Office of Technology Development, National Institute of Mental Health, Bethesda, Maryland, U.S; 2FDA, Division of Neurological and Physical Medicine Devices; Silver Spring, Maryland, U.S.; 3DARPA, Biological Technologies, Arlington, Virginia, U.S.; 4NSF, Division of Behavioral & Cognitive Sciences, Arlington, Virginia, U.S.

WORKSHOP 5 – BRAIN AND NANOTECHNOLOGY: STRATEGIES FOR EPSCOR AND OTHER MULTI-INVESTIGATOR, PROGRAMMATIC RESEARCH FUNDING

OPPORTUNITIES


Notes

BRAIN AND NANOTECHNOLOGY: STRATEGIES FOR EPSCOR AND OTHER MULTI-INVESTIGATOR, PROGRAMMATIC RESEARCH FUNDING OPPORTUNITIES


FRIDAY, DECEMBER 4, 2015ABSTRACTS


Notes

ADHESIVE FORCE BETWEEN GRAPHENE NANOSCALE FLAKES AND BIOLOGICAL CELLS

Radwan Al Faouri1, Ralph Henry2, and Gregory Salamo1

1Department of Physics, University of Arkansas, Fayetteville, Arkansas, U.S.; 2Department of Biological Sciences, University of Arkansas, Fayetteville, Arkansas, U.S.

Graphene, a two-dimensional layer of one atomic thickness of carbon, has proved to have a variety of possible biological and biomedical applications, such as glucose detection [1]. The main goal of this research is to quantify the adhesive force between graphene flakes and live cells. E.coli cells were selected in this investigation because E. coli naturally binds to the luminal surface of the intestinal tract and as humans we have millions of E.coli cells [2].

In this work, we used atomic force microscopy (AFM) to characterize the size of graphene flakes (functionalized and non-functionalized) sitting on either a substrate, such as silicon, or deposited on live cells, such as E.coli. More importantly, we used a significant AFM feature that allows us to measure the adhesive force between the AFM tip and the surface in order to quantitatively measure the adhesion between graphene and the cell wall of E.coli. More interestingly, using AFM enabled us to discriminate between the ability of graphene to attach to the cell wall of both live and dead E.coli based on graphene type whether it is functionalized or non-functionalized.

In addition, we will also discuss results and our basic understanding for both functionalized and non-functionalized graphene, live and dead cells, and as a function of the thickness of the graphene flakes.

Support has been provided by the Food and Drug Administration (FDA) and the state of Arkansas.

References

[1] Song, Y., et al., Graphene Oxide: Intrinsic Peroxidase Catalytic Activity and Its Application to Glucose Detection. Materials Views, 2010: p. 2206-2210.

[2] Law, R.J., et al., In Vitro and In Vivo Model Systems for Studying Enteropathogenic Escherichia coli Infections. Cold Spring Harb Perspectives in Medicine, 2013:

p. 1-17.

WORKSHOP ABSTRACTS

WORKSHOP 6 – ARKANSAS CONSORTIUM ON CARBON-BASED NANOSTRUCTURES: CARBON NANOTUBES, FULLERENES AND GRAPHENE


Notes

ADHESIVE FORCE BETWEEN GRAPHENE NANOSCALE FLAKES AND BIOLOGICAL CELLS


Notes

EVALUATION OF THE BIOACTIVITY OF GRAPHENE IN ESCHERICHIA COLI

Sakshi Rampal, Ananya Sharma, David McNabb, Ralph Henry, and Ravi D. Barabote

Department of Biological Sciences, University of Arkansas, Fayetteville, Arkansas, U.S.

Rapid advances in nanotechnology necessitate assessment of the safety of nanomaterial in the resulting products and applications. One key nanomaterial attracting much interest in many areas of commerce is graphene. Research on the bioactivity of nanomaterial, such as graphene, has very high significance for human health as well as the environment. We evaluated the biological effects of functionalized and non-functionalized graphene on Escherichia coli, a prokaryotic model organism. To dissect the various effects of graphene exposure in E. coli, we used (1) Spot Test to assess growth inhibition, (2) RNAseq to understand changes in the whole transcriptome, (3) Fluctuation Assay to evaluate the rate of spontaneous mutations and (4) Whole Genome Sequencing to study mutations in DNA. Spot Test analysis revealed that functionalized graphene inhibited the growth of E. coli at concentrations greater than 80 µg/ml. RNAseq analysis of the whole transcriptome of E. coli revealed that functionalized graphene substantially affected the expression of approximately 80 genes, including crucial genes involved in electron transport, sulfur metabolism, solute transport and genetic regulation. Fluctuation Assay analysis showed that functionalized graphene increased the rate of spontaneous mutations in E. coli. Whole Genome Sequencing of representative spontaneous mutants revealed DNA mutation patterns specific to functionalized graphene exposure. Overall, our data shows that functionalized graphene is cytotoxic and genotoxic to E. coli.


Notes

EVALUATION OF THE BIOACTIVITY OF GRAPHENE IN ESCHERICHIA COLI


Notes

ASSESSMENT OF GRAPHENE TOXICITY IN LIVE CELLS AND CELL SPHEROIDS USING DNASE ACTIVITY PROBE

Tariq Fahmi1, Zeid A. Nima2, Alena Savenka1, Julietta Sargsyan1, Alexandru S. Biris2, and Alexei G. Basnakian1,3

1Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.; 2University of Arkansas at Little Rock, Little Rock, Arkansas, U.S.; 3Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, U.S.

Graphene will likely be used widely because of its versatility. However, little is known about its potential for being a toxicant and environmental hazard, and methods to study graphene toxicity are yet to be established. We hypothesized that graphene, as many other toxicants, induces cytotoxicity mainly through DNA destruction and measuring of DNase activity in live cells by using oligonucleotide-based cell-permeable near infrared fluorescence (NIRF) DNase activity probe would be a reliable tool for assessing the graphene cytotoxicity. The hypothesis was first confirmed by the observation that non-modified graphene exposed with cultured rat kidney tubular epithelial NRK-52E cells induced TUNEL-type DNA fragmentation in a dose-dependent manner. Surface Enhanced Raman Spectroscopy (SERS) showed that TUNEL-positive cells have significantly higher graphene content than TUNEL-negative cells. Quantitative immunocytochemistry (qICC) was then used to measure apoptotic DNases, such as caspase-activated DNase (CAD), endonuclease G (EndoG), and DNase I, and the marker of oxidative stress, heme oxygenase-1 (HO-1). The NIRF fluorescence and all of the used qICC markers were induced in the cells by graphene exposure. Furthermore, we developed kidney spheroid (mini-kidney) model by culturing NRK-52E cells using 3D hanging drop method and tested the graphene toxicity in this model by measuring the DNase activity using the NIRF probe. The result showed a strong dose-dependent increase of DNase activity induced by graphene. In summary, the measuring of DNase activity by using NIRF probe in combination with TUNEL assay and qICC may be useful tools for the assessment of graphene toxicity.


Notes

ASSESSMENT OF GRAPHENE TOXICITY IN LIVE CELLS AND CELL SPHEROIDS USING DNASE ACTIVITY PROBE


Notes

NANOPARTICLES FOR BRAIN CANCER THERAPY

Jacob Berlin

Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, California, U.S.

Even when treated with aggressive current therapies, most patients with primary or metastatic malignant brain tumors survive less than two years. Although immunotherapy is being studied as a potential treatment, the blood-brain barrier and local tumor immunosuppressive milieu may prevent penetration of cytotoxic antibodies or immune cells into the brain. Local delivery of immunostimulatory molecules, such as CpG, can overcome this suppressive environment, but at high doses may also cause toxic brain inflammation. Thus, there is a pressing need for a safer, more effective targeted strategy to enhance CNS immune responses to malignant brain tumors. Here we present our work on using carbon nanotube/CpG constructs for targeted immunotherapy and our associated work using iron oxide nanoparticles to control the movement of activated immune cells.


Notes

NANOPARTICLES FOR BRAIN CANCER THERAPY


Notes

THE IMPACT OF GRAPHENE BASED NANOMATERIALS ON PUBLIC HEALTH: SYNTHESIS, CHARACTERIZATION AND DETECTION OF GRAPHENE MATERIALS

Shawn E. Bourdo and Alexandru S. Biris, Ph.D.

University of Arkansas at Little Rock, Little Rock, Arkansas, U.S.

Nanomaterials have recently gained attention for their unique properties, morphology and wide variety of potential applications. Carbon-based nanomaterials, such as graphene, have become one of the most researched due to their use in electronics, energy conversion and storage, water purification and drug delivery. The bonding between carbons in pure graphene is an extensive network of sp2-bond structure resulting in a material that is highly hydrophobic and generally difficult to process. In order to make graphene more processible, it can be modified in order to combine with other materials more easily. Graphene materials are known as graphene oxide, reduced graphene oxide, graphene nanoplatelets, etc. These various types of graphene nanomaterials share similarities, but they also are distinctly different. In our lab we have generally made and characterized two types of oxidized graphene, or oxygen functionalized graphene: (1) with low oxygen content–90%C and 10%O and (2) high oxygen content– ~80%C and ~20%O. The high oxygen content graphene exhibits a predominance of carboxylic acid functional groups on the surface which can be modified by traditional organic chemistry techniques.

While these materials promise many exciting advances in technology and everyday life, they also demand an evaluation of their impact on the environment and public health. Over the last decade many routes have been developed for the synthesis of graphene briefly mentioned above, with a variety of different end products. It is imperative to understand the surface chemistry and structural aspects of graphenes when evaluating the impacts of these nanomaterials. To this end, our group has been focused on a variety of chemico-structural characterization techniques to evaluate graphene based nanomaterials. Specifically, X-ray photoelectron spectroscopy (elemental composition and bonding environments), Infrared spectroscopy (functional group analysis) and Raman spectroscopy (structural defects in carbon lattice) will be discussed. Additionally, recent data generated in our lab allows for the detection of minute quantities of graphene at the cellular level by a Raman-based technique.


Notes

THE IMPACT OF GRAPHENE BASED NANOMATERIALS ON PUBLIC HEALTH: SYNTHESIS, CHARACTERIZATION AND DETECTION OF GRAPHENE MATERIALS


Notes

LOCAL AND SYSTEMIC IMMUNE SYSTEM RESPONSES TO INTRA-DERMALLY ADMINISTERED GRAPHENE-BASED NANOMATERIALS

Gisela F. Erf, Kallie Sullivan, and Hyeonmin Jang

University of Arkansas, Division of Agriculture, Department of Poultry Science, Fayetteville, Arkansas, U.S.

The skin and its derivatives are used extensively to examine cellular/tissue responses to test-materials. Working with the avian system, we developed a method using the growing feather (GF) as a dermal test-site (US-Patent 8,216,551). The living portion of a GF is a column of complex tissue (approx. 8-10 mm long, 2-3 mm diameter) that consists mostly of inner dermis (pulp) covered by epidermis. Intra-dermal injection of several GF with test-material and GF-collection at various times post-injection enables monitoring of local responses to test-materials in an individual. Using this in vivo test-system together with blood sampling, both the local and systemic (blood) responses to injection of 10 µL of functionalized graphene nanomaterial (GBN; 2.5 µg GBN/GF) or vehicle (PBS) (6 chickens/treatment; 20 GF/chicken) were examined before (0) and at 0.25, 1, 2, 3, 4, 5 and 7 days post-GF-injection. Blood and three GF were collected at each time-point; one GF was used to prepare pulp cell suspensions for immunofluorescent staining of leukocyte subsets, one was fixed in buffered-formalin for preparation of hematoxylin/eosin stained tissue sections, and one was snap-frozen for immunohistochemical staining. Compared to vehicle-injection, intra-dermal GBN-injection did not affect blood leukocyte concentrations and proportions. Based on flow cytometric pulp cell-analysis, intra-dermal injection of GBN resulted in leukocyte infiltration into GF with overall higher (main effect P < 0.05) levels (% pulp cells) of IgM+ B cells, gamma-delta T cells, CD4+ T cells and CD8+ lymphocytes compared to vehicle-injected controls. Preparation and evaluation of fixed and frozen GF tissue-sections is underway.


Notes

LOCAL AND SYSTEMIC IMMUNE SYSTEM RESPONSES TO INTRA-DERMALLY ADMINISTERED GRAPHENE-BASED NANOMATERIALS


Notes

LABEL-FREE QUANTIFICATION OF GRAPHENE NANOMATERIALS IN BIOLOGICAL SAMPLES USING PHOTOTHERMAL AND PHOTOACOUSTIC TECHNIQUES

D.A. Nedosekin and V.P. Zharov


Detailed characterization of interactions between potentially hazardous materials and living systems requires knowledge of material distribution and bioavailability. This is especially crucial for nanoparticles that are not dispersed homogeneously like molecular compounds and still can easily penetrate into live cells. Arkansas state universities and the FDA National Center of Toxicological Research in Jefferson, Arkansas, are collaborating on characterization of graphene-based nanomaterials (GBNs). The detection of GBNs consisting mainly of carbon atoms in biological samples is greatly hindered by carbon-rich sample matrix; chemical NP modifications dramatically change sample properties.

The Arkansas Nanomedicine laboratories pioneered the development of optical methods for label-free detection of non-fluorescent GBNs using photothermal (PT) and photoacoustic (PA) phenomena. These methods provide highly sensitive detection as in vitro among live cells, so as in vivo in animal mice models. We demonstrated that single flakes of GBNs can be detected with high sensitivity and specificity among cancer cells or in biological fluids like blood and lymph in vitro. We now report on advances in the development of in vivo GBNs quantification techniques for mouse blood and tissues. Our data revealed differences in circulation kinetics for GBNs having different surface chemistry and flake size. Noteworthy is the two stage clearance dynamic for GBNs introduced into mouse blood. Using multimodal detection with PA quantification of GBNs and fluorescence labeling of apoptosis we have developed a novel probe for in vivo assessment of toxic effects GBNs may have on circulating blood cells, clots formation and interactions with immune cells.


Notes

LABEL-FREE QUANTIFICATION OF GRAPHENE NANOMATERIALS IN BIOLOGICAL SAMPLES USING PHOTOTHERMAL AND PHOTOACOUSTIC TECHNIQUES


Notes

DEVELOPMENT OF NANOPLATFORMS FOR MOLECULAR IMAGING OF CANCER TARGETS

Dmitri Artemov

Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.

Targeted imaging agents provide increased sensitivity and specificity of detection. Magnetic nanoparticles can be used as highly sensitive MR imaging agents and as an additional advantage they can be used as carriers for image-guided therapy.

In this presentation the progress and major problems of designing targeted nanoplatforms for cancer imaging will be discussed for preclinical cancer models.

WORKSHOP 7 – NANOIMAGING AND NANONEUROIMAGING: SPECIAL FOCUS ON IMAGING MODALITIES THAT DETECT NANOMATERIALS, PRIMARILY MRI

(?MRI + X)


Notes

DEVELOPMENT OF NANOPLATFORMS FOR MOLECULAR IMAGING OF CANCER TARGETS


SCIENCE AS ART COMPETITION


SCIENCE AS ART JUDGES

Donald Bobbitt, Ph.D., is president of the University of Arkansas System. After earning a doctorate in chemistry from Iowa State University in 1985, Bobbitt became an assistant professor in the department of chemistry and biochemistry at the University of Arkansas. From 1988-93, he was a recipient of the Camille and Henry Dreyfus Foundation Teacher-Scholar Fellowship. His research program received support from national corporations and organizations including the R.W. Johnson Pharmaceutical Research Institute, the National Institutes of Health, the National Science Foundation, the U.S. Department of Agriculture and the Howard Hughes Medical Institute. He is also the author or co-author of 56 referenced publications and has been an invited speaker at meetings of the American Chemical Association. In 2003, he was named dean of the J. William Fulbright College of Arts and Sciences at the University of Arkansas. He became provost and vice president for academic affairs at the University of Texas at Arlington in 2008 and was selected to serve as president of the University of Arkansas System in 2011.

Deborah Baldwin, Ph.D., is the former dean of the UALR College of Arts, Humanities, and Social Sciences and currently is the associate provost of the UALR Division of Collections and Archives. She is formerly the chair of the department of history at UALR. She holds a doctorate from the University of Chicago and has authored several books and a variety of scholarly and popular articles primarily on modern Mexican history.

Bill Mitchell is president of MITCHELLworks, a company he founded in 2000 to provide personalized service to the nonprofit community in fundraising, fundraising feasibility and strategic planning. In addition to his role as president of MITCHELLworks, he is senior consultant for the North Group Inc., a planning and fundraising firm in New York, New York. He continues in both roles helping nonprofits throughout the United States acquire the help they need to plan for and to reach the levels of performance they seek. Mitchell was founding director of both the Walton Arts Center in Fayetteville, Arkansas, where he orchestrated a $10,000,000 fundraising campaign to complete the construction and to equip that center; and the Clay Center for the Arts & Sciences in Charleston, West Virginia. During his three-year tenure to build the Clay Center, Mitchell helped to raise over $40,000,000 toward accomplishing the center’s $128,000,000 dream. He also spent seven years as assistant director of ACUCAA (now Association of Performing Arts Presenters), was a board member for Arts Presenters, served as its president, was the 1990 National Conference co-chair and in 1996 he received the Fan Taylor Award for Distinguished Service to that organization.


SCIENCE AS ART SUBMISSIONS

TITLE: Multistage Vector (MSV)-parthenolide-nanoparticles for Treatment of Leukemia

DESCRIPTION: Multistage vector (MSV) particles system: (Upper) Graphic representation of the multistage delivery system. Blue particles with pink dots represent the micelles packed with parthenolide (for treatment of leukemia). Green strings represent E-selectin thioaptamers on the surface of the multistage particles as targeting moiety. Because there are so many thioaptamers on the surface, the whole area of the particle is colored in light green. (Lower) Confocal micrograph showing gH2AX foci (green), nuclear staining showing in blue.

SUBMITTED BY: Zaineb A. F. Albayati1, Hongliang Zong2, Siddhartha Sen2, Guodong Zhang3, David G. Gorenstein4, Xuewu Liu3, Mauro Ferrari3, Peter A. Crooks1, Gail J.

Roboz2, Haifa Shen3, and Monica L. Guzman2

AFFILIATION: 1Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas; 2Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, New York; 3Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, U.S.; 4Institute of Molecular Medicine, University of Texas-Houston Medical School, Houston, Texas, U.S.

TITLE: Three Dimensional in Fluid Image of Live E.coli Cells on a Glass Surface

DESCRIPTION: Technique that I used to obtain this image is Atomic Force Microscopy (AFM), where a tiny tip scans the surface and measures very small changes or features on the surface by recording the deflection of laser that is reflected from the tip. This image is unique because it was captured in fluid. The different sizes of E.coli cells are due to the difference in time division of these cells.

We would like to acknowledge professor Min Zou from the department of mechanical engineering/University of Arkansas, as well as the Food and Drug Administration (FDA) and the state of Arkansas for their support.

SUBMITTED BY: Radwan Al Faouri1, Ralph Henry2, and Gregory Salamo1

AFFILIATION: 1Department of Physics, University of Arkansas, Fayetteville, Arkansas, U.S.; 2Department of Biological Sciences, University of Arkansas, Fayetteville, Arkansas, U.S.


TITLE: Dark Field Imaging of Hemazoin in Malaria Infected RBCs

DESCRIPTION: It is a picture of red blood cells from a mouse that had been infected with malaria. I obtained the image using dark field microscopy (a light scattering technique we use to visualize nanoparticles in cells) looking at a RBC smear from the mouse. The goal was to obtain a dark field image of the hemozoin, a natural nanoparticle (heme crystal) that is produced as the hemoglobin of the RBCs is digested by the malaria parasite. Our lab

utilized the presence of this natural nanoparticle to detect malaria in the blood stream of infected mice.

SUBMITTED BY: Walter Harrington

AFFILIATION: Interdisciplinary Biomedical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.

TITLE: A Curious Day for the Nanobiologist

DESCRIPTION: Breast cancer cells were treated with anginex conjugated gold nanostructures, and the nucleus was stained. Cells were visualized using dark field microscopy (left) and epifluorescence (right). Au nanoparticles were visualized by transmission electron microscopy and one aggregate seemed to show a rather triumphant biologist.

SUBMITTED BY: Samir V. Jenkins

AFFILIATION: Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.

TITLE: Nanosilver Aggregates

DESCRIPTION: Image of Nanosilver on the JEM-2100 using a Gatan US4000 CCD camera operating at 200 kV. The image was processed with NIH ImageJ to highlight the artistic effect.

SUBMITTED BY: Nathan Koonce

AFFILIATION: NCTR Nanocore, U.S. Food and Drug Administration


TITLE: Assessing the Bioactivity of InP/ZnS Quantum Dot Nanoparticles in Cultured Chicken Macrophages

DESCRIPTION: Chicken macrophages treated with 0.2 micromolar indium phosphide zinc sulfide (InP/ZnS) quantum dot nanoparticles for 18 hours. This image is one of a series that was captured during my first experiment to determine whether these quantum dots would be taken up by the macrophages and could be imaged using our fluorescence imaging system. I was not only wonderfully surprised that I could visualize the particles, but

while I was making adjustments to exposures, filters, etc., I captured a few images at higher magnification that I thought were pretty striking visually.

SUBMITTED BY: Chris Lyle

AFFILIATION: Department of Poultry Science, University of Arkansas, Fayetteville, Arkansas, U.S.

TITLE: Iron in a Liver Box

DESCRIPTION: Serial Block Face Scanning Electron Microscopy of liver cells exposed to nano-iron oxide (FeO3). Images were recorded on a Zeiss Merlin with a Gatan 3View Serial Block Face sectioning device. Three thousand seven hundred and seventy nine images (3779) were recorded at 1.3 kV, 50 nm per slice and 5.8 nm/pixel in X and Y. Because an electron microscope records black and white images, the images were segmented using FEI’s Amira™ image processing software package. This was done to extract the 3D information from the 3D volume recorded with the 3View

system. The black and white images represent the X, Y and Z planes of the volume, with the segmented structures suspended against them. The yellow structure is the nucleus, the blue structure a vacuole, and the green structures the nano-iron oxide aggregates.

SUBMITTED BY: William Monroe

AFFILIATION: NCTR/FDA Nanocore, NCTR Office of Scientific Coordination, Jefferson Lab, Jefferson, Arkansas, U.S.


TITLE: 165 nm Rutile Titanium Oxide (TiO2) Nanoparticles Treated Primary Human Mesenchymal STEM Cells

DESCRIPTION: Human mesenchymal stem cells were grown to confluency in cell culture and treated with 165 nm Rutile TiO2 nanoparticles. The cells were first washed and then prepped for scanning electron microscopy (SEM). The purpose of the experiment was to evaluate the effectiveness of washing the TiO2 nanoparticles off prior to processing the cells to the next step in the study. This image was recorded using a Zeiss Merlin FEG

SEM operating at 5 kV accelerating voltage. The image was then scanned 6144 x 4608. The TiO2 nanoparticles were then artificially colored to bring out the contrast of the nanoparticles against the cells using first NIH ImageJ to isolate the nanoparticles from the cells and then CS6 Photoshop to mask those particles away from the original image. This allowed the regions containing the TiO2 to be colored separately from the background image of the cell. The colors only signify the average locations of Titanium nanoparticles.

SUBMITTED BY: Angel Paredes and Jia Yao

AFFILIATION: NCTR Nanocore, U.S. Food and Drug Administration

TITLE: Silver Nanobeads on a Biological Necklace

DESCRIPTION: Atomic force microscopy (AFM) of 20 nm silver nanoparticles associated with macromolecules from a human cell line.

SUBMITTED BY: Katherine Williams, Thilak Mudalige, Kuppan Gokulan, and Sangeeta Khare

AFFILIATION: National Center for Toxicological Research

1 0 0 N A N O T E C H N O L O G Y F O R H E A L T H C A R E C O N F E R E N C E - W I N T H R O P R O C K E F E L L E R I N S T I T U T E

1 0 2 N A N O T E C H N O L O G Y F O R H E A L T H C A R E C O N F E R E N C E - W I N T H R O P R O C K E F E L L E R I N S T I T U T E

december 2-4, 2015 · our program this year will focus on human disease diagnostics, therapeutics...

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