Nanobiotechnology

Part I: Applications & Markets

By

Prof. K. K. Jain MD, FRACS, FFPM

Jain PharmaBiotech

Basel, Switzerland

November 2018

A Jain PharmaBiotech Report

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A U T H O R ' S B I O G R A P H Y

Professor K. K. Jain is a neurologist/neurosurgeon by training and has been working in the biotechnology/biopharmaceuticals industry for several years. He received graduate training in both Europe and USA, has held academic positions in several countries and is a Fellow of the Faculty of Pharmaceutical Medicine of the Royal College of Physicians of UK. Currently he is a consultant at Jain PharmaBiotech. Prof. Jain’s 478 publications include 30 books (6 as editor + 24 as author) and 50 special reports, which have covered important areas in biotechnology, gene therapy and biopharmaceuticals. His books include "Role of Nanobiotechnology in Molecular Diagnostics" (2006), "Handbook of Nanomedicine" (Humana/Springer 2008; Chinese edition, Peking University Press 2011, 2nd ed Springer 2012, 3rd ed April 2017), “Textbook of Personalized Medicine (Springer 2009; Japanese ed 2012; 2nd ed Springer, 2015), "Handbook of Biomarkers" (Springer 2010; Chinese edition, Chemical Industry Press 2016, 2nd edition, 2017), Handbook of Neuroprotection (Springer 2011, 2nd edn 2019, in preparation), “Applications of Biotechnology in Cardiovascular Therapeutics” (Springer 2011), “Applications of Biotechnology in Neurology” (Springer 2013), and “Applications of Biotechnology in Oncology” (Springer 2014). He has edited “Drug Delivery Systems”, 2nd ed (Springer 2014) and “Applied Neurogenomics” (Springer 2015). He is currently editing “Drug Delivery Systems”, 3rd ed (Springer 2019).

November 2018 (continuously published since 2004) Copyright © 2017 by

Jain PharmaBiotech Bläsiring 7 CH-4057 Basel Switzerland

Tel & Fax: +4161-6924461 Email: info@pharmabiotech.ch Web site: http://pharmabiotech.ch/

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, or otherwise without the prior written permission of the Publisher. This report may not be lent, resold or otherwise traded in any manner without the consent of the Publisher. While all reasonable steps have been taken to ensure the accuracy of the information presented, the Publisher cannot accept responsibility for inadvertent errors or omissions.

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T A B L E O F C O N T E N T S

0. EXECUTIVE SUMMARY ........................................................................... 23

1. Introduction ......................................................................................... 25 Basics of nanobiotechnology.............................................................................................. 25

European Union definition of nanomaterials ......................................................................... 26 Nanoscale time and light ................................................................................................... 27

Nanotime ................................................................................................................... 27 Nanolasers ................................................................................................................. 27

Nanomedicine .................................................................................................................... 27 Relation of nanobiotechnology to nanomedicine ................................................................ 28 Landmarks in the evolution of nanomedicine ..................................................................... 28 Nanomedicine as a part of evolution of medicine ............................................................... 29

2. Nanotechnologies ................................................................................. 31 Introduction ...................................................................................................................... 31 Classification of nanobiotechnologies ................................................................................ 31

Nanoparticles .................................................................................................................. 32 Gold nanoparticles ...................................................................................................... 33 Cubosomes ................................................................................................................ 33 Fluorescent nanoparticles ............................................................................................. 34 Fullerenes .................................................................................................................. 34 Graphene ................................................................................................................... 35 Magnetic nanoparticles ................................................................................................ 35 Nanoparticles assembly into micelles ............................................................................. 36 Nanoshells ................................................................................................................. 36 Plant-derived nanoparticles .......................................................................................... 36 Polymer nanoparticles ................................................................................................. 37 Porous silicon nanoparticles .......................................................................................... 37 Quantum dots ............................................................................................................ 37 Synthetic high density lipoprotein nanoparticles .............................................................. 38 Hybrid nanoparticles.................................................................................................... 38

Bacterial structures relevant to nanobiotechnology ............................................................... 39 Nanostructures based on bacterial cell surface layers ...................................................... 39 Bacterial magnetic particles .......................................................................................... 39

Carbon nanotubes ............................................................................................................ 40 Medical applications of nanotubes ................................................................................. 40

Dendrimers ..................................................................................................................... 41 Properties .................................................................................................................. 42 Applications................................................................................................................ 42

DNA nanostructures ......................................................................................................... 43 DNA origami ............................................................................................................... 43 Bacteriophages for mass production of DNA origami ........................................................ 43 Fractal assembly ......................................................................................................... 44 Gigadalton-scale structures .......................................................................................... 44 Nanobricks ................................................................................................................. 44 Advantages of DNA nanostructure ................................................................................. 44 Potential applications of DNA octahedron ....................................................................... 45

Nanowires ....................................................................................................................... 45 Nanopores ...................................................................................................................... 46 Nanoporous silica aerogel ................................................................................................. 46 Nanostructured silicon ...................................................................................................... 47 Nanoparticle conjugates .................................................................................................... 47

DNA-nanoparticle conjugates ........................................................................................ 47 Networks of gold nanoparticles and bacteriophage .......................................................... 47 Protein-nanoparticle combination .................................................................................. 48

Polymer nanofibers .......................................................................................................... 48 Virus-like particles ........................................................................................................... 49

Measurement of nanoparticle size and distribution ........................................................... 49 Nanomaterials for biolabeling ............................................................................................ 50

DNA Nanotags ................................................................................................................. 51 Fluorescent lanthanide nanorods ........................................................................................ 51 Magnetic nanotags ........................................................................................................... 52 Molecular computational identification ................................................................................ 52 Nanophosphor labels ........................................................................................................ 52 Organic nanoparticles as biolabels ...................................................................................... 53 Quantum dots as labels .................................................................................................... 54 SERS nanotags ................................................................................................................ 54 Silica nanoparticles for labeling antibodies .......................................................................... 54

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Silver nanoparticle labels .................................................................................................. 55 Micro- and nano-electromechanical systems ..................................................................... 55

BioMEMS......................................................................................................................... 56 Microarrays and nanoarrays .............................................................................................. 56

Dip Pen Nanolithography for nanoarrays ............................................................................. 57 Applications of dip-pen nanolithography ......................................................................... 57

Protein nanoarrays ........................................................................................................... 58 Single-molecule protein arrays ..................................................................................... 58

Microfluidics and nanofluidics ............................................................................................ 58 Nanotechnology on a chip ................................................................................................. 59 Microfluidic chips for nanoliter volumes ............................................................................... 60 Use of nanotechnology in microfluidics ............................................................................... 60

2D nanofluidics ........................................................................................................... 60 Construction of nanofluidic channels .............................................................................. 60 Nanoscale flow visualization ......................................................................................... 61 Moving (levitation) of nanofluidic drops with physical forces ............................................. 61 Electrochemical nanofluid injection ................................................................................ 62 Nanofluidics on nanopatterned surfaces ......................................................................... 62 Nano-interface in a microfluidic chip .............................................................................. 62 Nanofluidic channels for study of DNA ........................................................................... 62

Visualization and manipulation on nanoscale .................................................................... 63 3D single-molecule microscopy with nanoscale accuracy ....................................................... 63 4Pi microscope ................................................................................................................ 63 Atomic force microscopy ................................................................................................... 64

AFM basics ................................................................................................................. 64 Advantages of AFM...................................................................................................... 64 AFM as nanorobot ....................................................................................................... 64 Force sensing Integrated Readout and Active Tip ............................................................ 65

AFM infrared spectroscopy ................................................................................................ 65 Cantilever technology ....................................................................................................... 65 CytoViva® Microscope System .......................................................................................... 67 Fluorescence Resonance Energy Transfer ............................................................................ 67 Fluorescence by Unbound Excitation from Luminescence ....................................................... 67 Magnetic resonance force microscopy and nanoscale MRI...................................................... 67 Multiple single-molecule fluorescence microscopy ................................................................ 68 Near-field scanning optical microscopy ............................................................................... 68 Nano-sized light source for single cell endoscopy ................................................................. 69 Nanoparticle characterization by Nanosight LM10 technology ................................................. 69 Nanoscale scanning electron microscopy ............................................................................. 70

Use of SEM to reconstruct 3D tissue nanostructure .......................................................... 70 Optical Imaging with a Silver Superlens .............................................................................. 70 Partial wave spectroscopy ................................................................................................. 71 Photoactivated localization microscopy ............................................................................... 71 Scanning probe microscopy ............................................................................................... 72 Single-molecule photon localization microscopy ................................................................... 72 STED microscopy ............................................................................................................. 72 Super-resolution microscopy for in vivo cell imaging ............................................................ 73

3D-SIM ...................................................................................................................... 73 Nanomicroscopy for live cell tomography ....................................................................... 73 RESOLFT Nanoscopy.................................................................................................... 74

Ultra-nanocrystalline diamond ........................................................................................... 74 Visualizing atoms with high-resolution transmission electron microscopy ................................ 75

Surface plasmon resonance ............................................................................................... 75 Nanotechnology and phototherapy .................................................................................... 76

3. Nanotechnologies for Basic Research Relevant to Medicine .................. 78 Introduction ...................................................................................................................... 78 Nanotechnology and biology .............................................................................................. 78

NanoSystems Biology ....................................................................................................... 78 Nanobiology and the cell ................................................................................................... 79

Biosensing of cellular responses .................................................................................... 80 Control of T cell signaling activity .................................................................................. 80 Measuring mass of single cells ...................................................................................... 81 Nanostructures involved in endocytosis .......................................................................... 81 Nanoparticles for in vivo study of cells ........................................................................... 81 Nanotechnology-based live-cell single molecule assays .................................................... 82 Quantum dots for stem cell labeling .............................................................................. 82 Quantum dot/antibody conjugates for in vivo cytometric imaging ...................................... 82 Quantum dots for study of apoptosis ............................................................................. 82 Ribosome as a Brownian nanomachine .......................................................................... 83 Single cell injection by nanolasers ................................................................................. 83

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Study of complex biological systems.............................................................................. 83 Tissue-engineering for studying effects of nanoparticles on cells ....................................... 84

Molecular motors ............................................................................................................. 84 Nanomotor made of nucleic acids .................................................................................. 86 phi29 DNA packaging nanomotor .................................................................................. 86 Light-activated ion channel molecular machines .............................................................. 87

Application of AFM for biomolecular imaging ........................................................................ 87 Future insights into biomolecular processes by AFM ......................................................... 88

4Pi microscopy to study DNA double-strand breaks .............................................................. 88 Nanoscale DNA imaging .................................................................................................... 88 Multi-isotope imaging mass spectrometry ........................................................................... 89 Applications of biomolecular computing in life sciences ......................................................... 89 Bacteria for construction of nanomachines .......................................................................... 90 Natural nanocomposites.................................................................................................... 90 Nanotechnology in biological research ................................................................................ 91

QDs for biological research ........................................................................................... 91 Molecular biology and nanotechnology ................................................................................ 92

Structural DNA nanotechnology .................................................................................... 92 RNA nanotechnology ................................................................................................... 93 Genetically engineered proteins for nanobiotechnology .................................................... 94

Single molecule studies .................................................................................................... 94 3D single-molecular imaging by coherent X-ray diffraction imaging ................................... 94 Nanoscale NMR for imaging single molecules .................................................................. 95 Optical trapping and single-molecule fluorescence ........................................................... 95 Study of molecular assembly of single molecules in living cells ......................................... 95

Nanochemistry ................................................................................................................... 96 Nanoscale pH Meter ......................................................................................................... 96

Nanolaser applications in life sciences ............................................................................... 96 Nanoelectroporation .......................................................................................................... 97 Nanomanipulation ............................................................................................................. 98

Atomic force microscopy ................................................................................................... 98 DNA nanomanipulation ..................................................................................................... 98 Fluorescence-force spectroscopy ........................................................................................ 98 Nanomanipulation by combination of AFM and other devices ................................................. 99

Surgery on living cells using AFM with nanoneedles ......................................................... 99 Manipulation of DNA sequence by use of nanoparticles as laser light antennas ....................... 100 Nanomanipulation of single molecule ................................................................................ 100 Nanomanipulation for study of mechanism of anticancer drugs ............................................ 100 Optoelectronic tweezers .................................................................................................. 101 Optical manipulation of nanoparticles ............................................................................... 101

Nanotechnology in genomic research .............................................................................. 102 Nanotechnology for separation of DNA fragments .............................................................. 102 Nanotechnology-based DNA sequencing ............................................................................ 102 Role of nanobiotechnology in identifying single nucleotide polymorphisms ............................. 104

Nanobiotechnology for study of mitochondria ................................................................. 104 Nanomaterials for the study of mitochondria ..................................................................... 104 Study of mitochondria with nanolaser spectroscopy ............................................................ 104

Nanoproteomics ............................................................................................................... 105 Biochips for nanoscale proteomics .................................................................................... 105

Protein biochips based on fluorescence planar wave guide technology ............................. 105 Nanofilter array chip .................................................................................................. 106

Dynamic reassembly of peptides ...................................................................................... 106 High-field asymmetric waveform ion mobility mass spectrometry ......................................... 106 Manipulation of redox systems by nanotechnology ............................................................. 107 Multi Photon Detection .................................................................................................... 107 Nanoflow liquid chromatography ...................................................................................... 107 Nanoparticle-protein interactions ..................................................................................... 107 Nanopore-based protein sequencing ................................................................................. 108 Nanopores for phosphoprotein analysis ............................................................................. 108 Nanoproteomics for study of misfolded proteins ................................................................. 108 Nanotube electronic biosensor for proteomics .................................................................... 109 Protein nanocrystallography ............................................................................................ 109 Protein engineering on nanoscale ..................................................................................... 109

Nanowires for protein engineering ............................................................................... 109 A nanoscale mechanism for protein engineering ............................................................ 110 Role of nanoparticles in self-assembly of proteins ......................................................... 110 Role of nanotechnology in peptide engineering ............................................................. 110

QD-protein nanoassembly ............................................................................................... 111 Single cell nanoprobe for studying gene expression of individual cells ................................... 111

Single cell nanoproteomics ......................................................................................... 111 Study of proteins by atomic force microscopy .................................................................... 111

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Study of proteomics at single molecule level ..................................................................... 112 Assays for protein expression at the single molecule level .............................................. 112 Imaging proteins at the single-molecule level ............................................................... 112 Mass spectrometry of single-molecules using nanotechnology ........................................ 113 Study of protein synthesis and single-molecule processes .............................................. 113

Role of nanotechnology in study of membrane proteins ...................................................... 114 Nanoparticles for study of membrane proteins .............................................................. 114 Study of single protein interaction with cell membrane .................................................. 114 Quantum dots to label cell surface proteins .................................................................. 115 Study of single membrane proteins at subnanometer resolution...................................... 115

Self-assembling peptide scaffold technology for 3D cell culture ............................................ 115 Nanobiotechnology and ion channels ............................................................................... 116

AFM for characterization of ion channels ........................................................................... 116 Aquaporin water channels ............................................................................................... 116 Nanopatch™ for study of ion channels at single molecule level ............................................ 117 Remote control of ion channels through magnetic-field heating of nanoparticles .................... 117 Role of nanobiotechnology in engineering ion channels ....................................................... 117

Nanobiotechnology for single cell analysis ...................................................................... 119 Nanotechnology and bioinformatics ................................................................................. 119

3D nano-map of synapse ................................................................................................ 119

4. Nanomolecular Diagnostics ................................................................ 121 Introduction .................................................................................................................... 121 Nanodiagnostics .............................................................................................................. 121

Rationale of nanotechnology for molecular diagnostics ........................................................ 123 Nanoarrays for molecular diagnostics .............................................................................. 123

Fullerene photodetectors for chemiluminescence detection on microfluidic chip ...................... 123 Microfluidics and nanotech tools for single cell analysis ....................................................... 123 Nanofluidic/nanoarray devices to detect a single molecule of DNA ........................................ 124 Protein nanoarrays ......................................................................................................... 125 Protein nanobiochip ........................................................................................................ 125 Silver nanorod array for on-chip detection of microbes and chemicals .................................. 125

AFM for molecular diagnostics ......................................................................................... 126 Nanofountain AFM probe ................................................................................................. 126 AFM for immobilization of biomolecules in high-density microarrays ..................................... 126 AFM for nanodissection of chromosomes ........................................................................... 126

Nanoparticles for molecular diagnostics .......................................................................... 127 3DNA® Dendrimers for diagnostics .................................................................................. 127 Carbon nanotubes .......................................................................................................... 127 Exosome-based molecular diagnostics .............................................................................. 127 Gold nanoparticles ......................................................................................................... 128 Quantum dots for molecular diagnostics ........................................................................... 128

QDs for detection of pathogenic microorganisms ........................................................... 129 Bioconjugated QDs for multiplexed profiling of biomarkers ............................................. 129 Imaging of living tissue with QDs ................................................................................ 129

Use of nanocrystals in immunohistochemistry .................................................................... 130 Magnetic nanoparticles ................................................................................................... 130

Magnetic nanoparticles for bioscreening ....................................................................... 130 Monitoring of implanted NSCs labeled with nanoparticles ............................................... 131 Perfluorocarbon nanoparticles to track therapeutic cells in vivo ....................................... 131 Superparamagnetic nanoparticles for cell tracking ......................................................... 131 SPIONS for real-time tracking of viral delivery .............................................................. 132 SPIONs for calcium sensing ........................................................................................ 132 Magnetic nanoparticles for labeling molecules ............................................................... 132 Study of living cells by SPIONs ................................................................................... 133

Imaging applications of nanoparticles ............................................................................... 133 CT image enhancement by nanoparticles ..................................................................... 133 Dendritic nanoprobes for imaging of angiogenesis ......................................................... 134 Functionalized MWCNTs as ultrasound contrast agents................................................... 134

Nanoparticles as contrast-enhancing agents for MRI ........................................................... 134 Gadolinium-loaded dendrimer nanoparticles for tumor-specific MRI ................................. 135 Gadonanotubes for MRI ............................................................................................. 135 Gold nanorods and nanoparticles as imaging agents ...................................................... 135 In vivo imaging using nanoparticles............................................................................. 136 Manganese oxide nanoparticles as contrast agent for brain MRI ...................................... 136 Magnetic nanoparticles as contrast agents for MRI of pancreas ....................................... 136 Nanoparticles as contrast agent for MRI ....................................................................... 136 Optical molecular imaging using targeted magnetic nanoprobes ...................................... 137 QDs for biological imaging .......................................................................................... 137 SPIONs combined with MRI ........................................................................................ 138 Concluding remarks and prospects of nanoparticles for imaging ...................................... 139

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Applications of nanopore technology for molecular diagnostics....................................... 139 Nanopore technology for detection of single DNA molecules ................................................ 139 Nanocytometry .............................................................................................................. 139

DNA-protein and -nanoparticle conjugates ...................................................................... 140 Resonance Light Scattering technology ........................................................................... 140 Nanobarcodes technology ................................................................................................ 141

Nanobarcode particle technology for SNP genotyping ......................................................... 141 QD nanobarcode for multiplexed gene expression profiling .................................................. 142 Biobarcode assay for proteins .......................................................................................... 142 Single-molecule barcoding system for DNA analysis ........................................................... 144

Nanoparticle-based colorimetric DNA detection method .................................................. 144 Nanoparticle-based up-converting phosphor technology ................................................. 145 Surface-Enhanced Resonant Raman Spectroscopy ........................................................... 145 Near-infrared (NIR)-emissive polymersomes .................................................................. 146 Nanobiotechnology for detection of proteins ................................................................... 146

Captamers with proximity extension assay for proteins ....................................................... 146 Immunoliposome-PCR .................................................................................................... 147

Nanobiosensors ............................................................................................................... 147 Cantilevers as biosensors for molecular diagnostics ............................................................ 147

Advantages of cantilever technology for molecular recognition ........................................ 148 Antibody-coated nanocantilevers for detection of microorganisms ................................... 149

Carbon nanotube biosensors ........................................................................................... 149 Carbon nanotube sensors coated with ssDNA and electronic readout ............................... 150 Carbon nanotubes sensors wrapped with DNA and optical detection ................................ 150

FRET-based DNA nanosensor ........................................................................................... 151 Graphene biosensor based on Raman spectroscopy ............................................................ 151 Ion channel switch biosensor technology ........................................................................... 151 Electrochemical nanobiosensor ........................................................................................ 151 Electronic nanobiosensors ............................................................................................... 152 Metallic nanobiosensors .................................................................................................. 152 Nanomaterial-based sensors for diagnosis from exhaled breath ........................................... 153 Quartz nanobalance biosensor ......................................................................................... 153 Viral nanosensor ............................................................................................................ 153 PEBBLE nanosensors ...................................................................................................... 154 Detection of cocaine molecules by nanoparticle-labeled aptasensors..................................... 154 Nanosensors for glucose monitoring ................................................................................. 154 Nanobiosensors for protein detection ................................................................................ 155 Optical biosensors .......................................................................................................... 155

Laser nanosensors .................................................................................................... 155 Interferometric reflectance imaging sensors ................................................................. 156 Nanoshell biosensors ................................................................................................. 156 Plasmonics and SERS nanoprobes ............................................................................... 156 Optical mRNA biosensors ........................................................................................... 157 Surface Enhanced Microoptical Fluidic Systems ............................................................. 157 Nanoparticle-enhanced sensitivity of fluorescence-based biosensors ................................ 158

Nanowire biosensors ...................................................................................................... 158 Nanowire biosensors for detection of cancer biomarkers ................................................ 159 Nanowire biosensors for detection of single viruses ....................................................... 160 Nanowires for detection of genetic disorders................................................................. 160 Nanowires biosensor for detecting biowarfare agents ..................................................... 160 Concluding remarks and prospects of nanowire biosensors ............................................. 160

Future issues in the development of nanobiosensors .......................................................... 161 Applications of nanodiagnostics....................................................................................... 161

Nanotechnology for detection of biomarkers ...................................................................... 161 Nanotechnology for genotyping of single-nucleotide polymorphisms ..................................... 162

Nanoparticles for detecting SNPs................................................................................. 162 Nanopores for detecting SNPs ..................................................................................... 162

Nanobiotechnologies for single molecule detection ............................................................. 163 Protease-activated QD probes ......................................................................................... 163 Labeling of MSCs with QDs .............................................................................................. 164 Nanotechnology for point-of-care diagnostics .................................................................... 164

Nanoswitch-linked immunosorbent assay ..................................................................... 165 Nanotechnology-based biochips for POC diagnosis ........................................................ 165 Carbon nanotube transistors for genetic screening ........................................................ 165 POC monitoring of vital signs with nanobiosensors ........................................................ 166 Nanodiagnostics for the battle field and biodefense ....................................................... 166 NANOANTENNA project of European Commission .......................................................... 167

Nanodiagnostics for integrating diagnostics with therapeutics .............................................. 167 Concluding remarks about nanodiagnostics ..................................................................... 167 Clinical trials of nanodiagnostics ..................................................................................... 168 Future of nanodiagnostics ............................................................................................... 169

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5. Nanopharmaceuticals ......................................................................... 170 Introduction .................................................................................................................... 170 Nanobiotechnology for drug discovery ............................................................................ 170

Nanofluidic devices for drug discovery .............................................................................. 171 Gold nanoparticles for drug discovery ............................................................................... 172

Tracking drug molecules in cells .................................................................................. 172 SPR with colloidal gold particles .................................................................................. 172

Use of QDs for drug discovery ......................................................................................... 172 Advantages of the use of QDs for drug discovery .......................................................... 172 Drawbacks of the use of QDs for drug discovery ........................................................... 173 QDs for imaging drug receptors in the brain ................................................................. 174

Lipoparticles for drug discovery ....................................................................................... 174 Biosensor for drug discovery with Lipoparticles ............................................................. 174

Magnetic nanoparticles assays ......................................................................................... 175 Analysis of small molecule-protein interactions by nanowire biosensors ................................ 175 Cells targeting by nanoparticles with attached small molecules ............................................ 175 Role of AFM for study of biomolecular interactions for drug discovery ................................... 176 Nanoscale devices for drug discovery ............................................................................... 176

Laboratories-on-a-chip .............................................................................................. 176 Lab-on-Bead ............................................................................................................ 176 Nanotechnology for drug design at cellular level ........................................................... 177

Role of nanobiotechnology in the future of drug discovery ................................................... 177 Nanobiotechnology-based drug development .................................................................. 177

Dendrimers as drugs ...................................................................................................... 177 Fullerenes as drug candidates .......................................................................................... 178 Nanobodies ................................................................................................................... 179

RANbodies ............................................................................................................... 180 Companies involved in nanobodies .............................................................................. 181

Preclinical studies of nanoparticles in animals and humans ............................................ 181 Manufacture of nanomedicines ........................................................................................ 182

Role of nanobiotechnology in microbial biofabrication ......................................................... 182 Nanobiotechnology in drug delivery ................................................................................ 182

Ideal properties of material for drug delivery ..................................................................... 182 Improved absorption of drugs in nanoparticulate form ........................................................ 183 Interaction of nanoparticles with human blood ................................................................... 183 Nanoscale devices delivery of therapeutics ........................................................................ 183 Nanobiotechnology solutions to the problems of drug delivery ............................................. 183 Nanocomposites for protein delivery ................................................................................. 184 Nanocomposite membranes for magnetically triggered drug delivery .................................... 184 Nanosuspension formulations .......................................................................................... 184 Nanotechnology-based refilling of drug delivery depots through circulation ........................... 185 Self-assembled nanostructures with hydrogels for drug delivery .......................................... 186 Nanomaterials and nanobiotechnologies used for drug delivery ............................................ 186

Viruses as nanomaterials for drug delivery ...................................................................... 187 Bacteria-mediated delivery of nanoparticles and drugs into cells .................................... 187

Bacterial viral membranes ............................................................................................... 188 Cell-penetrating peptides ................................................................................................ 189 Nanoparticle-based drug delivery .................................................................................... 189

Cationic nanoparticles..................................................................................................... 190 Ceramic nanoparticles .................................................................................................... 190 Cyclodextrin nanoparticles for drug delivery ...................................................................... 190 Dendrimers for drug delivery ........................................................................................... 191

DNA-assembled dendrimers for drug delivery ............................................................... 191 DNA tetrahedron-based drug delivery system .................................................................... 192 Exosomes for drug delivery ............................................................................................. 192 Fullerenes for drug delivery ............................................................................................. 193

Amphiphilic fullerene derivatives ................................................................................. 193 Fullerene conjugates for intracellular delivery of peptides ............................................... 193

Gold nanoparticles as drug carriers .................................................................................. 193 Layered double hydroxide nanoparticles ........................................................................... 194 Micelles for drug delivery ................................................................................................ 194 Nanocrystals ................................................................................................................. 195

Nanocrystalline silver ................................................................................................ 195 Elan's NanoCrystal technology .................................................................................... 195 Biorise system .......................................................................................................... 196

Nanodiamonds ............................................................................................................... 197 Polymer nanoparticles .................................................................................................... 197

Biodegradable PEG nanoparticles for penetrating the mucus barrier ................................ 198 PLGA-based nanodelivery technologies ........................................................................ 198 Polymeric micelles ..................................................................................................... 198 Chitosan nanoparticles ............................................................................................... 199

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QDs for drug delivery ..................................................................................................... 200 Special procedures in nanoparticle-based drug delivery ...................................................... 200

Coated nanoparticles for penetrating cell membranes without damage ............................ 200 Combinatorial synthesis of nanoparticles for intracellular delivery ................................... 200 Drug delivery using “Particle Replication in Nonwetting Templates” ................................. 200 Encapsulating water-insoluble drugs in nanoparticles ..................................................... 201 Filomicelles vs spherical nanoparticles for drug delivery ................................................. 201 Flash NanoPrecipitation .............................................................................................. 202 Magnetic nanoparticles for drug delivery ...................................................................... 202 Nanoparticles bound together in spherical shapes ......................................................... 203 Perfluorocarbon nanoparticles for imaging and targeted drug-delivery ............................. 203 Prolonging circulation of nanoparticles by attachment to RBCs ........................................ 204 Self-assembling nanoparticles for intracellular drug delivery ........................................... 204 Trojan nanoparticles .................................................................................................. 205 Therapeutic protein delivery from nanoparticle-protein complexes .................................. 205 Triggered release of drugs from nanoparticles .............................................................. 205

Liposomes ........................................................................................................................ 206 Basics of liposomes ........................................................................................................ 206 Stabilization of phospholipid liposomes using nanoparticles ................................................. 206 Lipid nanoparticles ......................................................................................................... 207

Advantages of the lipid nanoparticle technology ............................................................ 207 Applications of lipid nanoparticles ................................................................................ 208 Arsonoliposomes ....................................................................................................... 208 Lipid nanocapsules .................................................................................................... 209 Lipid emulsions with nanoparticles .............................................................................. 209 Polymerized liposomal nanoparticle ............................................................................. 210 Solid lipid nanoparticles ............................................................................................. 210

Nanostructured organogels ............................................................................................. 210 Niosomes ...................................................................................................................... 211 Limitations of liposomes for drug delivery ......................................................................... 211 Liposomes incorporating fullerenes ................................................................................... 211 Liposome-nanoparticle hybrids ........................................................................................ 211

Nanogels .......................................................................................................................... 212 Nanogel-liposome combination ........................................................................................ 212

Nanospheres .................................................................................................................... 212 Nanotubes ....................................................................................................................... 213

Carbon nanotubes for drug delivery ................................................................................. 213 CNT-liposome conjugates for drug delivery into cells .......................................................... 213 Lipid-protein nanotubes for drug delivery .......................................................................... 214 Halloysite nanotubes for drug delivery .............................................................................. 214

Nanocochleates ............................................................................................................... 215 Nanobiotechnology and drug delivery devices ................................................................. 215

Nano-encapsulation ........................................................................................................ 215 Nanotechnology-based device for insulin delivery ............................................................... 216 Nanoporous materials for drug delivery devices ................................................................. 216

Nanopore membrane in implantable titanium drug delivery device .................................. 216 Measuring the permeability of nanomembranes ............................................................ 217

Nanovalves for drug delivery ........................................................................................... 217 Nanochips for drug delivery ............................................................................................. 217

Nanobiotechnology-based transdermal drug delivery ...................................................... 218 Introduction .................................................................................................................. 218 Delivery of nanostructured drugs from transdermal patches ................................................ 218 Effect of mechanical flexion on penetration of bucky balls through the skin ........................... 219 Ethosomes for transdermal drug delivery .......................................................................... 219 NanoCyte transdermal drug delivery system ..................................................................... 220 Safety issues of applications of nanomaterial carriers on the skin ......................................... 220 Transdermal administration of lipid nanocapsules ............................................................... 220 Transdermal nanoparticle preparations for systemic effect .................................................. 221

Nasal drug delivery using nanoparticles .......................................................................... 221 Mucosal drug delivery with nanoparticles ........................................................................ 222 Future prospects of nanotechnology-based drug delivery................................................ 222

DNA nanorobots for drug delivery .................................................................................... 223 Nanomolecular valves for controlled drug release ............................................................... 223 Nanosponge for drug delivery .......................................................................................... 223 Nanomotors for drug delivery .......................................................................................... 223

6. Role of Nanotechnology in Biological Therapies .................................. 225 Introduction .................................................................................................................... 225 Nanotechnology for delivery of proteins and peptides ..................................................... 225 Nanobiotechnology for vaccine delivery .......................................................................... 225

Bacterial spores for delivery of vaccines ............................................................................ 225

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Dendrimer-RNA nanoparticle vaccines .............................................................................. 226 Lipid nanoparticles for immunostimulatory RNA delivery ..................................................... 226 Nanoparticles for DNA vaccines ........................................................................................ 226 Nanoparticle-based adjuvants for vaccines ........................................................................ 226 Nanospheres for controlled release of viral antigens ........................................................... 227 Nanotechnology-based mucosal vaccines .......................................................................... 228 Nanotechnology for oral vaccines ..................................................................................... 228 Proteosomes™ as vaccine delivery vehicles ....................................................................... 228 Targeted Synthetic Vaccine Particle (tSVP™) technology ..................................................... 228 Virus-mimetic nanovesicles as an antigen-delivery system .................................................. 229

Nanobiotechnology for cell therapy ................................................................................. 229 Nano-biocomposites containing living cells ........................................................................ 230

Nanobiotechnology for gene therapy ............................................................................... 230 Nanoparticle-mediated gene therapy ................................................................................ 230

Calcium phosphate nanoparticles as nonviral vectors ..................................................... 232 Carbonate apatite nanoparticles for gene delivery ......................................................... 232 Dendrimers for gene transfer...................................................................................... 232 DNA nanoparticles ..................................................................................................... 233 Gelatin nanoparticles for gene delivery ........................................................................ 233 Immunoliposomes for delivery anticancer gene therapy ................................................. 234 Lipid nanoparticles for targeted delivery of nucleic acids ................................................ 234 Magnetic nanoparticles for targeted gene delivery ......................................................... 235 Nanoparticles for imaging and intracellular delivery of nucleic acids ................................. 235 Nanoparticles linked to viral vectors for photothermal therapy ........................................ 235 Nanoparticles for p53 gene therapy of cancer ............................................................... 235 Nanoparticles with virus-like function as gene therapy vectors ........................................ 236 Nanobiolistics for nucleic acid delivery ......................................................................... 236 Photo-controlled in vivo activation of biomolecules by nanoparticles ................................ 236 Silica nanoparticles for gene delivery ........................................................................... 237

Cochleate-mediated DNA delivery .................................................................................... 237 Nanorod gene therapy .................................................................................................... 238 Nanomagnets for targeted cell-based cancer gene therapy .................................................. 238 NanoNeedles for delivery of genetic material into cells ........................................................ 238 Application of pulsed magnetic field and superparamagnetic nanoparticles ............................ 239

Nanobiotechnology for antisense drug delivery ............................................................... 239 Antisense nanoparticles .................................................................................................. 239 Dendrimers for antisense drug delivery ............................................................................. 240 Polymer nanoparticles for antisense delivery system .......................................................... 240

Nanoparticle-mediated siRNA delivery ............................................................................. 240 Chitosan-coated nanoparticles for siRNA delivery ............................................................... 240 Delivery of siRNA by nanosize liposomes ........................................................................... 241 Delivery of gold nanorod-siRNA nanoplex to dopaminergic neurons ...................................... 241 Polymer-based nanoparticles for siRNA delivery ................................................................. 241

Polyethylenimine nanoparticles for siRNA delivery ......................................................... 241 siRNA-PEG nanoparticle-based delivery ........................................................................ 242 Polycation-based nanoparticles for siRNA delivery ......................................................... 242 Calando's technology for targeted delivery of anticancer siRNA ....................................... 243 Self-assembling nanoplatform for delivery of siRNA ....................................................... 243 Topical delivery of siRNA-nanoparticle conjugates ......................................................... 244

Quantum dots to monitor RNAi delivery ............................................................................ 244 RNAi-based nanomedicines for gene silencing in hematological malignancies ......................... 244

Lipid nanoparticles for mRNA delivery ............................................................................. 245

7. Nanodevices & Techniques for Clinical Applications ........................... 246 Introduction .................................................................................................................... 246 Clinical nanodiagnostics .................................................................................................. 246

Nano-endoscopy ............................................................................................................ 246 Application of nanotechnology in radiology ........................................................................ 247 High-resolution ultrasound imaging using nanoparticles ...................................................... 247

Nanobiotechnology in tissue engineering ........................................................................ 248 Nanoscale surfaces for stem cell culture............................................................................ 248 3D nanofilament-based scaffolds ..................................................................................... 248 Electrospinning technology for nanobiofabrication .............................................................. 249 Nanomaterials for tissue engineering ................................................................................ 250

Carbon nanotubes for artificial muscles ........................................................................ 250 Nanofibers for tissue engineering of skeletal muscle ...................................................... 250

Nanofibrous scaffolds for stem cell-based regenerative therapies ......................................... 250 Nanomaterials for combining tissue engineering and drug delivery ....................................... 251

Nanobiotechnology for organ replacement and assisted function .................................... 251 Exosomes for drug-free organ transplants ......................................................................... 252 Nanobiotechnology and organ-assisting devices ................................................................. 252

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Nanosurgery .................................................................................................................... 253 Miniaturization in surgery ................................................................................................ 253

Nanotechnology for hemostasis during surgery ............................................................. 253 Minimally invasive surgery using catheters ........................................................................ 253

Nanorobotics ................................................................................................................... 254 In vivo microbot propulsion ............................................................................................. 254 Nanorobots ................................................................................................................... 255

Nanoscale laser surgery................................................................................................... 255

8. Nanooncology ..................................................................................... 258 Introduction .................................................................................................................... 258 Nanobiotechnology for detection of cancer ...................................................................... 258

Aptasensor for electrochemical detection of exosomes ........................................................ 258 Aptamer-nanoparticle combinations for cancer diagnostics and therapeutics .......................... 258 Dendrimers for sensing cancer cell apoptosis ..................................................................... 259 Detection of circulating cancer cells .................................................................................. 259

DNA nanospheres for isolation of CTCs ........................................................................ 259 Magnetic nanoparticles for capturing CTCs ................................................................... 260 Nano-Velcro technology for capturing CTCs .................................................................. 260

Gold nanoparticles for cancer diagnosis ............................................................................ 260 Gold nanorods for detection of metastatic tumor cells ......................................................... 262 Magnetoacoustic detection of cancer using superparamagnetic nanoparticles ........................ 262 Nanosensors for cancer diagnosis .................................................................................... 262

Differentiation between normal and cancer cells by nanosensors ..................................... 262 Implanted biosensor for cancer ................................................................................... 262

Nanotubes for detection of cancer proteins ........................................................................ 263 Nanobiochip sensor technique for analysis of oral cancer biomarkers ............................... 263 Nanodots for tracking apoptosis in cancer .................................................................... 264 Nanolaser spectroscopy for detection of cancer in single cells ......................................... 264 Nanoparticles designed for dual-mode imaging of cancer ............................................... 264 Nanotechnology-based single molecule assays for cancer ............................................... 264 QDs for detection of tumors ....................................................................................... 265 QD-based test for DNA methylation ............................................................................. 265 Spectral imaging and CNTs in malignant tumors ........................................................... 266

Nanobiotechnology for early detection of cancer to improve treatment ................................. 266 Nanobiotechnology-based drug delivery in cancer ........................................................... 267

Nanoparticle formulations for drug delivery in cancer ......................................................... 268 Anticancer drug particles incorporated in liposomes ....................................................... 268 Cerasomes ............................................................................................................... 269 Doxorubicin nanocarriers ........................................................................................... 269 Curcumin nanoformulation as cancer therapeutics ......................................................... 270 Encapsulating drugs in hydrogel nanoparticles .............................................................. 271 Exosomes ................................................................................................................ 271 Folate-linked nanoparticles ......................................................................................... 272 Ginger nanoparticles for delivery of chemotherapy in colorectal cancer ............................ 272 Gold nanoparticles stabilized with resveratrol ............................................................... 272 Iron oxide nanoparticles ............................................................................................ 272 Lipid based nanocarriers ............................................................................................ 273 Micelles for drug delivery in cancer .............................................................................. 273 Minicells for targeted delivery of nanoscale anticancer therapeutics ................................. 274 Protein nanocages for penetration of airway mucous and tumors .................................... 275 Nanoconjugates for subcutaneous delivery of anticancer drugs ....................................... 275 Nanomaterials for delivery of poorly soluble anticancer drugs ......................................... 276 Nanoparticle formulation for enhancing anticancer efficacy of cisplatin ............................. 276 Nanoparticle formulations of paclitaxel......................................................................... 276 Nanoparticles containing albumin and antisense oligonucleotides .................................... 277 Nanorobots for anticancer drug delivery ....................................................................... 277 Niosomes for anticancer drug delivery ......................................................................... 278 Pegylated nanoliposomal formulation ........................................................................... 278 Peptide-linked nanoparticle delivery ............................................................................ 278 Poly-2-hydroxyethyl methacrylate nanoparticles ........................................................... 279 Polypeptide-doxorubicin conjugated nanoparticles ......................................................... 279 Porous silicon nanoparticles for cancer drug delivery ..................................................... 279 Protosphere nanoparticle technology ........................................................................... 280 siRNA delivery in combination with nanochemotherapy .................................................. 280 Zinc oxide nanoparticles for drug delivery in cancer....................................................... 280

Nanoparticles for targeted delivery of anticancer therapeutics ............................................. 281 Aptamer nanoformulations for targeted anticancer therapy ............................................ 281 Bacteriophage capsid-based nanoparticles for targeted cell-delivery ................................ 282 Canine parvovirus as a nanocontainer for targeted drug delivery .................................... 282 Carbon nanotubes for targeted drug delivery to cancer cells ........................................... 283

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Carbon magnetic nanoparticles for targeted drug delivery in cancer ................................ 283 Chitosan nanoparticles for targeted anticancer drug delivery .......................................... 284 CRLX101 for targeted anticancer drug delivery ............................................................. 284 Cyclosert system for targeted delivery of anticancer therapeutics.................................... 284 Fullerenes for enhancing tumor targeting by antibodies ................................................. 284 Gold nanoparticles for targeted drug delivery in cancer .................................................. 285 Hepatic artery infusion of LDL-DHA nanoparticles for liver cancer .................................... 286 Hyaluronic acid nanocarriers for targeted anticancer therapeutics ................................... 287 Magnetic nanoparticles for remote-controlled drug delivery to tumors ............................. 287 Mesoporous silica nanoparticles .................................................................................. 288 Monitoring of targeted delivery by nanoparticle-peptide conjugates ................................. 288 Nanobees for targeted delivery of cytolytic peptide melittin ............................................ 288 Nanobody-shell polymeric micelles for targeted drug delivery ......................................... 289 Nanocarrier-based targeted delivery od RNAi-based therapy .......................................... 289 Nanoformulations of monoclonal antibodies for targeted drug delivery ............................. 289 Nanogel-based stealth cancer vaccine targeting macrophages ........................................ 290 Nanovehicles for targeted delivery of paclitaxel............................................................. 290 Nanocell for targeted drug delivery to tumor ................................................................ 291 Nanodiamonds for local delivery of chemotherapy at site of cancer ................................. 291 Nanoimmunoliposome-based system for targeted delivery of siRNA ................................ 292 Nanoparticle-mediated targeting of MAPK signaling pathway .......................................... 292 Nanoparticles for targeted antisense therapy of cancer .................................................. 292 Nanoparticles for delivery of suicide DNA to prostate tumors .......................................... 293 Nanoparticles for targeted delivery of concurrent chemoradiation .................................... 293 Nanoparticle-based therapy targeted to cancer metastases ............................................ 293 Nanoparticle-mediated delivery of multiple anticancer agents ......................................... 294 Nanostructured hyaluronic acid for targeted drug delivery in cancer ................................ 294 Perfluorocarbon emulsion for targeted chemotherapeutic delivery ................................... 294 Polymer nanoparticles for targeted drug delivery in cancer ............................................. 295 Polymersomes for targeted cancer drug delivery ........................................................... 296 Quantum dots and quantum rods for targeted drug delivery in cancer ............................. 296 Remote controlled drug delivery from magnetic nanocrystals.......................................... 297 Targeted delivery of nanoparticulate drugs into lymphatic system ................................... 297 Targeted drug delivery with nanoparticle-aptamer bioconjugates .................................... 297 Use of T cells for delivery of gold nanoparticles to tumors .............................................. 298

Dendrimers for anticancer drug delivery ........................................................................... 298 Application of dendrimers in boron neutron capture therapy ........................................... 299 Application of dendrimers in photodynamic therapy ....................................................... 300 Dendrimer-based synthetic vector for targeted cancer gene therapy ............................... 300 Poly-L-lysine dendrimer as antiangiogenetic agent ........................................................ 301

RNA nanotechnology for delivery of cancer therapeutics ..................................................... 301 Delivery of siRNAs for cancer ...................................................................................... 301

Combination delivery systems for nanoparticle penetration into tumor tissue ........................ 302 Nanotechnology-based cancer therapy ............................................................................ 302

Devices for nanotechnology-based cancer therapy ............................................................. 302 Convection-enhanced delivery with nanoliposomal CPT-11 ............................................. 302 Nanoengineered silicon for brachytherapy .................................................................... 303

Anticancer effect of nanoparticles ..................................................................................... 303 Antiangiogenic therapy using nanoparticles .................................................................. 303 Cytotoxic effects of cancer nanoparticles ...................................................................... 303 Gold nanoparticles for inhibiting tumor growth .............................................................. 304 Nanoshell-based cancer therapy ................................................................................. 304 Nanobody-based cancer therapy ................................................................................. 304

Nanosecond pulsed electric fields for cancer therapy .......................................................... 305 Nanoparticles combined with physical agents for tumor ablation .......................................... 305

Boron neutron capture therapy using nanoparticles ....................................................... 305 Gold nanoparticles combined with radiation therapy ...................................................... 306 Laser-induced cancer destruction using nanoparticles .................................................... 306 Nanoparticle-mediated thermal ablation of cancer ......................................................... 308 Temperature-sensitive liposomes for cancer destruction ................................................ 310 Ultrasound radiation of tumors combined with nanoparticles .......................................... 310

Nanomedicines combined with molecular targeted anticancer therapeutics ............................ 311 Bispecific nanobioconjugate for targeted cancer immunotherapy ..................................... 311

Impact of nanotechnology-based imaging in management of cancer .................................... 311 Cornell dots for cancer imaging ................................................................................... 311 Nanoparticles and optoacoustic imaging in management of cancer .................................. 312 Nanoparticle-MRI for tracking dendritic cells in cancer therapy ....................................... 313 Nanoparticle-CT scan ................................................................................................. 313 Nanosensor device as an aid to cancer surgery ............................................................. 313 Nanoparticle-based imaging in oncology clinical trials .................................................... 314 QDs aid lymph node mapping in cancer ....................................................................... 314

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Single wall carbon nanotubes for targeted imaging of tumors ......................................... 314 Nanoparticles for targeted therapy of tumors .................................................................... 315 Nanocarriers with TGF-β inhibitors for targeting cancer ....................................................... 315 Nanobombs for cancer .................................................................................................... 315 Nanoparticle-based anticancer drug delivery to overcome MDR ............................................ 316

Time-delayed, dual-drug nanoparticle delivery system ................................................... 316 Combination of diagnostics and therapeutics for cancer ...................................................... 317

Aptamer conjugated magnetic nanoparticles................................................................. 317 Biomimetic nanoparticles targeted to tumors ................................................................ 317 Dendrimer nanoparticles for targeting and imaging tumors ............................................ 318 Gold nanoparticle plus bombesin for imaging and therapy of cancer ................................ 318 Gold nanorods for diagnosis plus photothermal therapy of cancer ................................... 318 Gold nanotubes for diagnosis plus photothermal therapy of cancer .................................. 319 Magnetic nanoparticles for imaging as well as therapy of cancer ..................................... 319 Micelles for targeted drug delivery and PET imaging in cancer ........................................ 320 Nanobialys for combining MRI with delivery of anticancer agents .................................... 320 Nanoparticles, MRI and thermal ablation of tumors ....................................................... 320 pHLIP nanotechnology for detection and targeted therapy of cancer ................................ 321 QD conjugates combine cancer imaging, therapy and sensing ........................................ 321 Silica nanoparticles for combining diagnosis with cancer therapy ..................................... 321 Squalene-based nanocomposites for tumor imaging and therapy .................................... 322 Radiolabeled carbon nanotubes for tumor imaging and targeting .................................... 322 Ultrasonic tumor imaging and targeted chemotherapy by nanobubbles ............................ 322

Role of nanobiotechnology in cancer immunology .............................................................. 323 Nanorobotics for management of cancer ........................................................................... 324

Bacterial nanorobots for targeting cancer ..................................................................... 324 DNA robots for targeting cancer .................................................................................. 324

Fullerenes for protection against chemotherapy-induced cardiotoxicity ................................. 325 Concluding remarks and future of nanooncology ................................................................ 325

9. Nanoneurology ................................................................................... 327 Introduction .................................................................................................................... 327 Nanobiotechnology for neurophysiological studies .......................................................... 327

Nanoelectrodes in neurophysiology .................................................................................. 327 Chronic EEG recording .................................................................................................... 327 Nanoscale devices for network-level electrophysiology ........................................................ 327 Chronic subcellular recording from implanted electrodes ..................................................... 328 Nanowires for monitoring brain activity via blood vessels .................................................... 328 Gold nanoparticles for in vivo study of neural function ........................................................ 329

Nanodiagnosis and nanoparticle-based brain imaging ..................................................... 329 Applications of nanotechnology in molecular imaging of the brain ........................................ 329 Nanoparticles and MRI for macrophage tracking in the CNS ................................................. 330 Nanoparticles for tracking stem cells for therapy of CNS disorders ....................................... 330 Multifunctional NPs for diagnosis and treatment of brain disorders ....................................... 331

Nanotechnology-based drug delivery to the CNS ............................................................. 331 Nanotechnology-based drug delivery for neurodegenerative disorders .................................. 331

Nanoencapsulation for delivery of vitamin E for Alzheimer disease .................................. 331 Selegiline-PEG nanoparticles targeting Aβ fibrils in Alzheimer disease .............................. 331

Nanoparticles for drug delivery across BBB ....................................................................... 331 Carbon nanotubes for drug delivery to the CNS ............................................................ 332 Nanoagonists of adenosine receptor for delivery across BBB ........................................... 333 Nanovesicles for transport across BBB ......................................................................... 333 Polymeric nanoparticles as carriers for CNS drug delivery .............................................. 334

Mechanism of the nanoparticle-mediated transport of the drugs across the BBB .................... 334 Transcytosis of transferrin-containing nanoparticles across the BBB ................................ 334

Nanotechnology-based strategies for drug delivery across BBB ............................................ 334 G-Technology® ........................................................................................................ 334 LipoBridge technology ............................................................................................. 335

Nanotechnology-based drug delivery to brain tumors ......................................................... 335 Intravenous gene delivery with nanoparticles into brain tumors ...................................... 335 Micelles for delivery of chemotherapy to brain tumors ................................................... 335 Multifunctional nanoparticles for treating brain tumors ................................................... 336 Nanoparticles for delivery of drugs to brain tumors across BBB ....................................... 336 NP delivery across the BBB for imaging and therapy of brain tumors ............................... 337 NP-based targeted delivery of chemotherapy across the BBB .......................................... 337 PLA nanoparticles for controlled delivery of BCNU to brain tumors ................................... 338

Nanoparticles as nonviral vectors for CNS gene therapy ...................................................... 338 Silica nanoparticles for CNS gene therapy .................................................................... 338 Cationic lipids for CNS gene therapy ............................................................................ 339 Polyethylenimine-based nanoparticles for CNS gene therapy .......................................... 339 Dendrimers for CNS gene therapy ............................................................................... 339

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Carbon nanotubes for CNS gene therapy ...................................................................... 339 Nanoparticle-based drug delivery to the inner ear .............................................................. 340 Nanotechnology-based devices and implants for CNS ......................................................... 340

Nanobiotechnology and neuroprotection ......................................................................... 340 Neuroprotection due to antioxidant effect of nanoparticles .................................................. 341 Neuroprotective nanoparticles that inhibit neuroinflammation .............................................. 342 Neuroprotective nanoparticles that inhibit Aβ formation ...................................................... 342

Nanobiotechnology for regeneration and repair of the CNS ............................................. 342 Nanowire neuroprosthetics with functional membrane proteins ............................................ 342 Nanotube-neuron electronic interface ............................................................................... 343 Role of nanobiotechnology in regeneration and repair following CNS trauma ......................... 343

Nanofibers as an aid to CNS regeneration by neural progenitor cells ................................ 343 Peptide nanostructures for repair of the CNS ................................................................ 344

Nanobiotechnology for repair and regeneration following TBI ............................................... 344 Nanoparticles for repair following SCI ............................................................................... 344

Repair of SCI by nanoscale micelles ............................................................................ 345 Nanobiotechnology-based devices for restoration of neural function ..................................... 345

Nanobiotechnology-based artificial retina ..................................................................... 345 Role of nanomedicine in treatment of neurodegenerative disorders ................................ 346 Nanopsychiatry ................................................................................................................ 346 Nanoneurosurgery ........................................................................................................... 346

Bucky balls for brain cancer ............................................................................................ 347 Electrospun nanofiber tubes for regeneration of peripheral nerves........................................ 347 Femtolaser neurosurgery ................................................................................................ 347 Graphene technology for neurosurgery ............................................................................. 348 Nanofiber brain implants ................................................................................................. 348

Nanoparticles as an aid to neurosurgery ...................................................................... 348 Nanoscaffold for CNS repair ............................................................................................ 349

Application of nanobiotechnology to pain therapeutics.................................................... 349

10. Nanocardiology ........................................................................... 351 Introduction .................................................................................................................... 351 Nanotechnology-based cardiovascular diagnosis ............................................................. 351

Detection of biomarkers of myocardial infarction in saliva by a nanobiochip ........................... 351 Nanobiosensors for detection of cardiovascular disorders .................................................... 351 Use of magnetic NPs as MRI contrast agents for cardiac imaging ......................................... 351 Perfluorocarbon NPs for combining diagnosis with therapy in cardiology ................................ 352 Cardiac monitoring in sleep apnea.................................................................................... 352 Detection and treatment of atherosclerotic plaques in the arteries ....................................... 352 Monitoring for disorders of blood coagulation ..................................................................... 353

Nanotechnology-based therapeutic delivery in cardiology ............................................... 353 Combination of diagnostics with therapeutics .................................................................... 353 Controlled delivery of nanoparticles to injured vasculature .................................................. 354 Nanobiotechnology-based therapeutic delivery in myocardial ischemia ................................. 354

IGF-1 delivery by nanofibers for cell therapy of myocardial infarction .............................. 355 Injectable peptide nanofibers for myocardial ischemia ................................................... 355

Liposomal nanodevices for targeted cardiovascular drug delivery ......................................... 355 Low molecular weight heparin-loaded polymeric nanoparticles ............................................. 356 Magnetic antibody-linked nanoparticles to deliver cells to the heart ...................................... 356 Nanoparticles for cardiovascular imaging and targeted drug delivery .................................... 356 Nanofiber-based scaffolds with drug-release properties ...................................................... 357 NP-based systemic drug delivery to prevent cardiotoxicity .................................................. 357 Targeted nanoparticle-DNA delivery to the cardiovascular system ........................................ 357

Nanotechnology-based therapeutics for cardiovascular diseases .................................... 358 Nanolipoblockers for atherosclerotic arterial plaques........................................................... 358 Nanoparticle-mediated drug delivery for atherosclerotic heart disease .................................. 358 Nanotechnology approach to the vulnerable plaque as cause of cardiac arrest ....................... 358

Nanotechnology for regeneration of the cardiovascular system ...................................... 359 Nanotechnology for cardiac revascularization .................................................................... 359 Nanocomposite hydrogels for myocardial tissue engineering ................................................ 359

Nanotechnology-based stents .......................................................................................... 360 Restenosis after percutaneous coronary angioplasty ........................................................... 360

Drugs encapsulated in biodegradable nanoparticles ....................................................... 361 Magnetic nanoparticle-coated DES .............................................................................. 361 Magnetic nanoparticles encapsulating paclitaxel targeted to stents .................................. 362 Nanocoated DES ....................................................................................................... 362 Nanopores to enhance compatibility of DES .................................................................. 363

Application of nanotechnology in cardiac catheterization ................................................ 363

11. Nanopulmonology ....................................................................... 365 Introduction .................................................................................................................... 365

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Nanoparticles for pulmonary drug delivery ...................................................................... 365 Systemic drug delivery via pulmonary route ...................................................................... 365 Nanoparticle drug delivery for effects on the respiratory system .......................................... 365 Fate and toxicology of nanoparticles delivered to the lungs ................................................. 366 Nanoparticle drug formulations for spray inhalation ............................................................ 366 Nanobiotechnology for improving insulin delivery in diabetes ............................................... 367

Inhalation of glucose-sensitive NP for regulated release of insulin ................................... 367 Pulmonary delivery of insulin by surface acoustic wave technology .................................. 367

Nanotechnology-based pharmaceuticals for pulmonary disorders ......................................... 367 Nanotechnology-based treatment of pulmonary disorders .............................................. 369

Management of cystic fibrosis .......................................................................................... 369 Nanobiotechnology-based gene transfer in CF ................................................................... 369

Nonviral DNA nanoparticle-mediated CFTR gene transfer ............................................... 369 Liposome-mediated CFTR gene transfer ....................................................................... 370 Magnetofection for enhancing nonviral gene transfer to the airways ................................ 370

NP-based delivery of antibiotics for treatment of pulmonary infections in CF .......................... 370 Nanotechnology-based treatment of chronic obstructive pulmonary disease .......................... 371 Nanotechnology-based treatment of pulmonary inflammation .............................................. 371

12. Nanoorthopedics ......................................................................... 373 Introduction .................................................................................................................... 373

Application of nanotechnology for bone research ................................................................ 373 Reducing reaction to orthopedic implants .......................................................................... 373 Enhancing the activity of bone cells on the surface of orthopedic implants ............................ 374 Synthetic nanomaterials as bone implants......................................................................... 374

NanoBone implants ................................................................................................... 374 NanoBone versus BioOss ............................................................................................ 375

Nanoparticles for repairing bone cracks ............................................................................ 375 Nanotechnology-based bone regeneration ......................................................................... 375

Delivery of growth factors for bone repair and regeneration ........................................... 375 Role of nanoparticles in regenerative therapy for osteoporosis ........................................ 376

Aligning nanotubes to improve artificial joints .................................................................... 376 Carbon nanotubes as scaffolds for bone growth ................................................................. 376 Nanoparticle-based hydrogels for cartilage regeneration ..................................................... 377 Nanotechnology for engineering of cartilage replacement .................................................... 377 Cartilage disorders of knee joint ...................................................................................... 378

Nanotechnology as an aid to arthroscopy ..................................................................... 378 Nanotechnology-based therapy for osteoarthritis .......................................................... 379

13. Nanoophthalmology .................................................................... 381 Introduction .................................................................................................................... 381

Nanocarriers for ocular drug delivery ................................................................................ 381 Dendrimers for drug delivery in ophthalmology ............................................................. 382 DNA nanoparticles for nonviral gene transfer to the eye ................................................. 382 Nanoparticle-based topical drug application to the eye ................................................... 382 Lipid nanoparticles for ocular drug delivery .................................................................. 383 Nanoparticles for intraocular drug delivery ................................................................... 383

Nanoparticles impregnated ocular inserts for drug delivery to the eye .................................. 384 Ophthalmic drug delivery through nanoparticles in contact lenses ........................................ 384 Nanotechnology-based therapeutics for eye disorders ......................................................... 384

Nanotechnology for prevention of neovascularization ..................................................... 385 Nanoparticles as nonviral vectors for gene therapy of retinal disorders ............................ 386 Nanobiotechnology for treatment of glaucoma .............................................................. 386 Nanotechnology for treatment for age-related macular degeneration ............................... 387

14. Nanomicrobiology ....................................................................... 389 Introduction .................................................................................................................... 389 Nanodiagnosis of infections ............................................................................................. 389

Detection of viruses ....................................................................................................... 389 Cantilever beams for detection of single virus particles .................................................. 389 Carbon nanotubes-based detection of viruses ............................................................... 389 Electric fields for accelerating detection of viruses ......................................................... 390 QD fluorescent probes for detection of respiratory viral infections ................................... 390 Verigene Respiratory Virus Plus Assay ......................................................................... 391 Surface enhanced Raman scattering for detection of viruses ........................................... 392

Detection of bacteria ...................................................................................................... 392 Nanoparticle-based methods for bacterial detection ....................................................... 392 QDs for detection of bacterial infections ....................................................................... 393

Role of nanobiotechnology in diagnosis of fungal infections ................................................. 393 Magnetic nanoparticle-based technique for detection of fungi ......................................... 393 Nano-amplification technique for the detection of fungal pathogens................................. 394

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Role of nanobacteria in human diseases .......................................................................... 394 Nature of nanobacteria ................................................................................................... 394 Nanobacteria and kidney stone formation ......................................................................... 395 Nanobacteria in cardiovascular disease ............................................................................. 395

Nanotechnology-based microbicidal agents ..................................................................... 396 Carbon nanotubes as antimicrobial agents ........................................................................ 396 Gold and silver nanoparticles as antibacterial agents .......................................................... 396 Gold nanoparticles for targeting drug-resistant bacteria ...................................................... 396 Nanocarriers for antibacterial peptides .............................................................................. 397 Nanoemulsions as microbicidal agents .............................................................................. 397 Nanoparticles for overcoming antibiotic resistance ............................................................. 397 Nanoformulations of antifungal agents .............................................................................. 398 Nanoscale bactericidal powders ....................................................................................... 398 Nanotubes for detection and destruction of bacteria ........................................................... 399 Nanoscale surface structure for antibacterial defense ......................................................... 399

Silver nanoparticle coating as prophylaxis against infection ............................................ 400 Nanobiotechnology and virology ...................................................................................... 400

Study of interaction of nanoparticles with viruses ............................................................... 400 Study of pathomechanism of viral diseases ....................................................................... 400 Transdermal nanoparticles for immune enhancement in HIV ............................................... 401 Nanofiltration to remove viruses from plasma transfusion products ...................................... 401

Nanotechnology-based antiviral agents ........................................................................... 402 Dendrimer-based intracellular delivery of antibodies ........................................................... 402 Dendrimers as nonviral vectors in dendritic cell-based immunotherapies ............................... 402 Fullerenes as antiviral agents .......................................................................................... 402 Gold nanorod-based delivery of RNA antiviral therapeutics .................................................. 403 Nanocoating for antiviral effect ........................................................................................ 403 Nanoviricides ................................................................................................................. 403 Nanocarrier-mediated siRNA delivery for treatment of HIV/AIDS .......................................... 405 Silver nanoparticles as antiviral agents ............................................................................. 406 siRNA lipid nanoparticle for the treatment of Ebola virus infection. ....................................... 406

15. Miscellaneous Healthcare Applications of Nanobiotechnology .... 409 Introduction .................................................................................................................... 409 Nanoimmunology ............................................................................................................. 409

Fullerenes for interruption of allergic/immune response ...................................................... 409 Carbon nanoparticle-based immunomodulation .................................................................. 409 Systemic lupus erythematosus ........................................................................................ 410

Inflammatory diseases .................................................................................................... 410 Rheumatoid arthritis ....................................................................................................... 410

Nanohematology .............................................................................................................. 412 Artificial red cells ........................................................................................................... 412 Feraheme ..................................................................................................................... 412

Nanoparticle-based drug delivery for gastrointestinal disorders ..................................... 412 Ginger nanoparticles for IBS ............................................................................................ 412

Nanoparticles for targeted therapeutic delivery to the liver ............................................ 413 Nanonephrology .............................................................................................................. 413

Nanobiotechnology-based renal dialysis ............................................................................ 413 Nanotechnology-based human nephron filter for renal failure ......................................... 414 Blood-compatible membranes for renal dialysis ............................................................ 414 Ceramic filter for renal dialysis ................................................................................... 414

Nanotechnology for wound healing ................................................................................. 414 Nanoengineered bandage for wound care .......................................................................... 415

Nanotechnology-based products for skin disorders ......................................................... 415 Cubosomes for treating skin disorders of premature infants. ............................................... 415 Nanoparticles for improving targeted topical therapy of skin ................................................ 416 Nanoparticle-based sun screens ....................................................................................... 416 Nanoengineered bionic skin ............................................................................................. 417 Topical nanocreams for inflammatory disorders of the skin .................................................. 417

Nanobiotechnology for disorders of aging ....................................................................... 417 Personal care products based on nanotechnology ........................................................... 418

Nanocosmeceuticals ....................................................................................................... 418 Nanotechnology for hair care ........................................................................................... 418

Nanodentistry .................................................................................................................. 419 Bonding materials .......................................................................................................... 419 Dental caries ................................................................................................................. 419 Nanospheres for dental hypersensitivity ............................................................................ 420 Nanomaterials for dental filling ........................................................................................ 420 Nanomaterials for dental implants .................................................................................... 420 Nanodiamonds for root canal repair .................................................................................. 421

Nanomedical aspects of oxidative stress ......................................................................... 421

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Nanoparticle antioxidants ................................................................................................ 421 Fullerene-based antioxidants ...................................................................................... 421 Ceria nanoparticles as neuroprotective antioxidants ...................................................... 422

Antioxidant nanoparticles for treating diseases due to oxidative stress ................................. 422 Nanotechnology and homeopathic medicines .................................................................. 422 Nanoparticles as antidotes for poisons ............................................................................ 423 Nanoparticles for chemo-radioprotection ........................................................................ 424 Role of nanobiotechnology in biodefense ......................................................................... 424

Nanoparticles to combat microbial warfare agents .............................................................. 424 Removal of toxins from blood .......................................................................................... 425

Nanobiotechnology for public health ............................................................................... 425 Nanotechnology for water purification ............................................................................... 425

Nanofiltration to remove viruses from water ................................................................. 426 Nanostructured membranes for water purification ......................................................... 426 Nanotechnologies for water remediation ...................................................................... 426 Nanotechnology-based photochemical water purification ................................................ 427 Magnetic nanoscavengers for water purification ............................................................ 427

Nanobiotechnology and nutrition ..................................................................................... 427 Nanobiotechnology and food industry ............................................................................... 428 Role of nanobiotechnology in personalized nutrition ........................................................... 429

16. Nanobiotechnology and Personalized Medicine ........................... 431 Introduction .................................................................................................................... 431 Role of nanobiotechnology in personalized management of cancer ................................. 432 Nanotechnology-based personalized medicine for cardiology .......................................... 433 Nanobiotechnology for therapeutics design and monitoring ............................................ 433

Smart nanosystems for personalized medicine ................................................................... 433 Nanosystems that respond to disease environments ...................................................... 434

17. Nanotoxicology ........................................................................... 435 Introduction .................................................................................................................... 435 Fate of nanoparticles in the human body ......................................................................... 435

Nanoparticle-protein interactions ..................................................................................... 435 Protein corona and nanoparticle toxicity ............................................................................ 435

Systemic toxicity of protein corona .............................................................................. 436 Protein corona and cytotoxicity ................................................................................... 436

Computational prediction of toxicity of nanosubstances .................................................. 436 In vitro vs in vivo testing for toxicity of nanoparticles ..................................................... 436

Stem cellines for testing toxicity of nanoparticles ............................................................... 437 Variations in safety issues of different nanoparticles ...................................................... 437

Carbon nanotube safety .................................................................................................. 437 Fullerene toxicity ........................................................................................................... 439 Gold nanoparticle toxicity ................................................................................................ 439 Graphene toxicity ........................................................................................................... 439 Quantum dot safety issues .............................................................................................. 439 Toxicity of gold nanoparticle as synergistic interaction with surfactants ................................. 440

Effects of nanoparticles on various body systems ............................................................ 441 Pulmonary effects of nanoparticles ................................................................................... 441 Neuronanotoxicology ...................................................................................................... 443

Nanoparticle deposits in the brain ............................................................................... 443 Nanoparticles and neurodegeneration .......................................................................... 443

Effect of nanoparticles on the heart .................................................................................. 444 Blood compatibility of nanoparticles ................................................................................. 444

Carbon nanoparticle-induced platelet aggregation ......................................................... 444 Compatibility of lipid-based nanoparticles with blood and blood cells ............................... 444

Transfer of nanoparticles from mother to fetus .................................................................. 445 Cytotoxicity of nanoparticles ........................................................................................... 445

Indirect DNA damage caused by nanoparticles across cellular barriers .................................. 446 Measures to reduce toxicity of nanoparticles ................................................................... 446

Reducing toxicity of carbon nanotubes .............................................................................. 446 A screening strategy for the hazard identification of nanomaterials ...................................... 447

Concluding remarks on safety issues of nanoparticles ..................................................... 447 Research into effects of nanoparticles in the environment .............................................. 447

Effect of magnetite pollution nanoparticles on the human brain ........................................... 448 Environmental safety of aerosols released from nanoparticle manufacture ............................ 448 Role of US government agencies in research on safety of nanoparticles ................................ 448 Work at NanoSafety Laboratories Inc UCLA ....................................................................... 449 Center for Biological and Environmental Nanotechnology .................................................... 449 European NEST project for risk assessment of exposure to nanoparticles .............................. 449

Nanoparticles and food safety ......................................................................................... 450 Titanium dioxide nanoparticles in food .............................................................................. 450

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Regulatory viewpoint on nanoparticles in food ................................................................... 451 Use of water nanostructures for inactivation of foodborne microorganisms ............................ 451

Public perceptions of the safety of nanotechnology ......................................................... 451 Evaluation of consumer exposure to nanoscale materials .................................................... 452

Safety of nanoparticle-based cosmetics ........................................................................... 453 Regulations in the European Union ................................................................................... 453 Nanotechnology-based sunscreens ................................................................................... 453 Cosmetic industry’s white paper on nanoparticles in personal care ....................................... 454 Skin penetration of nanoparticles used in sunscreens ......................................................... 454 Titanium dioxide in cosmetics .......................................................................................... 454

18. Ethical and Regulatory Aspects of Nanomedicine ........................ 455 Introduction .................................................................................................................... 455 Ethical and social implications of nanobiotechnology ...................................................... 455

Nanoethics .................................................................................................................... 455 Nanotechnology patents .................................................................................................. 456

Quantum dot patents relevant to healthcare applications .................................................... 457 Challenges and future of nanobiotechnology patents .......................................................... 457

Legal aspects of nanobiotechnology ................................................................................ 457 Nanotechnology standards .............................................................................................. 458 Preclinical testing of nanometerials for biological applications........................................ 459 FDA regulation of nanobiotechnology products ............................................................... 459

FDA and nanotechnology-based medical devices ................................................................ 461 FDA’s Nanotechnology Task Force .................................................................................... 462 FDA collaboration with agencies/organizations relevant to nanotechnology ............................ 463

Regulation of nanotechnology in the European Union ...................................................... 464 Safety recommendations of the Royal Society of UK ........................................................... 464 European Commission and safety of nanocosmetics ........................................................... 465

19. Research and Future of Nanomedicine ........................................ 466 Introduction .................................................................................................................... 466 Nanobiotechnology research in the academic centers ..................................................... 466 Clinical trials of nanomedicines ....................................................................................... 469 Future of nanomedicine ................................................................................................... 470 Support for nanobiotechnology by US Government agencies ........................................... 471

Nanomedicine initiative of NIH ......................................................................................... 471 US Federal funding for nanobiotechnology......................................................................... 471 NCI Alliance for Nanotechnology in Cancer ........................................................................ 472 Centers of Cancer Nanotechnology Excellence ................................................................... 472 Innovative Research in Cancer Nanotechnology ................................................................. 473 Manufacture of nanomedicines......................................................................................... 474 Nanotechnology Characterization Laboratory ..................................................................... 474 Nanomedicine Center for Nucleoprotein Machines .............................................................. 474

Global Enterprise for Micro-Mechanics and Molecular Medicine ....................................... 475 Nanomedicine in Europe .................................................................................................. 475

NANO2LIFE ................................................................................................................... 475 European Technology Platform on NanoMedicine ................................................................ 476 European Union’s “Horizon 2020” ..................................................................................... 476 European Nanomedicine Characterisation Laboratory .......................................................... 477

20. Nanobiotechnology Markets ........................................................ 478 Introduction .................................................................................................................... 478 Markets according to areas of applications ...................................................................... 479

Markets for nanomedicine ............................................................................................... 480 Markets for nanodiagnostics ............................................................................................ 480 Markets for biochips/microarrays ..................................................................................... 480 Imaging agents ............................................................................................................. 481 Pharmaceuticals............................................................................................................. 481

Role of nanobiotechnology in drug delivery market ........................................................ 481 Nanobiotechnology in life sciences research market............................................................ 482

Markets according to technologies .................................................................................. 482 Markets for nanomaterials ............................................................................................... 482 Markets for biomedical nanodevices ................................................................................. 482

Markets for nanosensors ............................................................................................ 483 Markets for nanotools ..................................................................................................... 483

Geographical distribution of markets ............................................................................... 483 Nanobiotechnology in the US ........................................................................................... 484 Nanobiotechnology in the European Union ...................................................................... 484

Nano2Life ..................................................................................................................... 486 European Technology Platform on NanoMedicine ................................................................ 486

Nanobiotechnology in Australia ....................................................................................... 487

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Nanobiotechnology in Asia ............................................................................................... 487 Japan ........................................................................................................................... 487 South Korea .................................................................................................................. 488 China ........................................................................................................................... 488 Taiwan ......................................................................................................................... 489 India ............................................................................................................................ 490

Nanobiotechnology in Russia ........................................................................................... 491 Nanobiotechnology in the developing world .................................................................... 491 Venture capital investment in nanotechnology ................................................................ 491 Big pharma and nanotechnology ...................................................................................... 492

Impact of nanobiotechnology on markets for current pharmaceuticals .................................. 492 Unmet needs in nanobiotechnology .................................................................................. 492

Drivers for the development of nanobiotechnology markets ............................................ 493 Strategies for developing markets for nanobiotechnology ............................................... 493

Collaborations of industry with academic research centers .................................................. 494 Collaborations of pharmaceutical and nanotechnology companies ........................................ 494 Collaboration of chemical industry and the government ...................................................... 494 Cost-benefit of nanotechnology-based drug delivery ........................................................... 495 Education of healthcare professionals ............................................................................... 495 Education of the public ................................................................................................... 495

21. References .................................................................................. 498

Tables

Table 1-1: Dimensions of various objects in nanoscale ................................................................... 25 Table 1-2: Historical landmarks in the evolution of nanomedicine .................................................... 28 Table 1-3: Nanomedicine in the 21st century ................................................................................ 30 Table 2-1: Classification of basic nanomaterials and nanobiotechnologies ......................................... 31 Table 2-2: Applications of S-layers in nanobiotechnology ................................................................ 39 Table 2-3: Potential applications of dendrimers in nanomedicine ...................................................... 42 Table 2-4: Nanomaterials for biolabeling ....................................................................................... 51 Table 2-5: Applications of cantilever technology ............................................................................ 66 Table 2-6: Applications of optical nanoscopy ................................................................................. 69 Table 3-1: Nanomaterials for the study of mitochondria ................................................................ 104 Table 4-1: Classification of applications of nanotechnologies in molecular diagnostics ....................... 122 Table 4-2: Nanobiotechnologies for single molecule detection........................................................ 163 Table 4-3: Clinical trials of nanodiagnostics ................................................................................. 168 Table 5-1: Basic nanobiotechnologies relevant to drug discovery ................................................... 171 Table 5-2: Companies involved in nanobodies ............................................................................. 181 Table 5-3: Nanomaterials used for drug delivery .......................................................................... 186 Table 5-4: Liposome-nanoparticle hybrid systems ........................................................................ 212 Table 6-1: Examples of application of nanoparticles for gene therapy ............................................. 231 Table 8-1: Classification of nanobiotechnology approaches to drug delivery in cancer ....................... 267 Table 8-2: Approved anticancer drugs using nanocarriers ............................................................. 268 Table 8-3: Bioavailability and anticancer effect of curcumin nanoformulations ................................. 270 Table 8-4: Aptamer-based nanoformulations for targeted anticancer therapy .................................. 281 Table 9-1: Neuroprotective nanoparticles .................................................................................... 340 Table 9-2: Role of nanobiotechnology in regeneration and repair following CNS trauma .................... 343 Table 9-3: Nanoparticles for targeted drug delivery in neurodegenerative disorders ......................... 346 Table 10-1: Nanobiotechnology-based therapeutic delivery in myocardial ischemia .......................... 354 Table 11-1: Pharmaceuticals incorporated into nanoparticle systems for pulmonary application. ........ 368 Table 13-1: Nanoparticles used for drug delivery in ophthalmology ................................................ 381 Table 13-2: Nanobiotechnology-based therapy of eye disorders ..................................................... 385 Table 15-1: Preclinical studies of nanomedicines for rheumatoid arthritis ........................................ 411 Table 15-2: Applications of nanotechnologies in food and nutrition sciences .................................... 427 Table 16-1: Examples of nanosystems that respond to disease environments.................................. 434 Table 18-1: FDA-approved nanotechnology based drugs ............................................................... 459 Table 19-1: Academic institutes/laboratories involved in nanobiotechnology ................................... 466 Table 19-2: Clinical trials of nanotechnology-based therapies ........................................................ 469 Table 20-1: Nanobiotechnology markets according to areas of application 2017-2027 ...................... 479 Table 20-2: Markets for nanobiotechnology according to technologies 2017-2027 ............................ 482 Table 20-3: Geographical distribution of nanobiotechnology markets 2017-2027 ............................. 483 Table 20-4: Drivers for the development of nanobiotechnology markets ......................................... 493 Table 20-5: Strategies for developing markets for nanobiotechnology ............................................ 494 Table 20-6: Cost-benefit of nanotechnology-based drug delivery ................................................... 495

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Figures

Figure 1-1: Sizes of biologically entities relevant to the brain .......................................................... 26 Figure 1-2:Relationship of various biotechnologies to nanomedicine ................................................. 28 Figure 2-1: The core, branching and surface molecules of dendrimers .............................................. 41 Figure 2-2: Imaging and size distribution of nanoparticles with TEM ................................................. 49 Figure 2-3: Schematic representation of Dip Pen Nanolithography (DPN) .......................................... 57 Figure 2-4: Surface plasmon resonance (SPR) technology ............................................................... 75 Figure 3-1: Concept of nanopore-based sequencing ..................................................................... 103 Figure 3-2: Nanopore-based sequence-specific detection of DNA ................................................... 103 Figure 4-1: Microfluidics and nanotech tools for single cell analysis ................................................ 124 Figure 4-2: Scheme of bio-barcode assay ................................................................................... 143 Figure 4-3: Scheme of an optical mRNA biosensor ....................................................................... 157 Figure 4-4: Nanowire biosensor for cancer diagnosis .................................................................... 159 Figure 4-5: DNA nanoswitch detection technique ......................................................................... 165 Figure 5-1: Application of nanobiotechnology at various stages of drug discovery ............................ 170 Figure 5-2: Bacteria plus nanoparticles for drug delivery into cells ................................................. 188 Figure 5-3: Schematic image of a lipid nanoparticle ..................................................................... 207 Figure 6-1: Nucleic acid delivery with lipid nanoparticle (LPN) technology ....................................... 234 Figure 6-2: Nanocochleate-mediated drug delivery ...................................................................... 238 Figure 8-1: Use of micelles for drug delivery ............................................................................... 273 Figure 8-2: Nanopore-based sequence-specific detection of DNA ................................................... 325 Figure 9-1: Nanodiagnostics for neurological disorders ................................................................. 329 Figure 9-2: A concept of targeted drug delivery to GBM across the BBB .......................................... 338 Figure 10-1: Magnetic nanoparticle-coated stent ......................................................................... 362 Figure 14-1: CNTs for improvement of detection and isolation of viruses ........................................ 390 Figure 14-2: Schematic representation of NanoViricide attacking a virus particle ............................. 404 Figure 14-3: Nanocarrier-mediated siRNA delivery for treatment of HIV/AIDS ................................. 406 Figure 16-1: Relationship of nanobiotechnology to personalized medicine ....................................... 431 Figure 16-2: Role of nanobiotechnology in personalized management of cancer ............................... 432 Figure 20-1: Components of the $1 trillion market for nanotechnologies in 2015 ............................. 478 Figure 20-2: Nanobiotechnology markets according to applications 2017-2027 ................................ 480 Figure 20-3: Geographical distribution of nanobiotechnology markets 2017-2027 ............................ 484 Figure 20-4: Unmet needs in nanobiotechnology applications ........................................................ 493