Amila.A.DissanayakeAmila.A.DissanayakeDepartment of ChemistryDepartment of Chemistry

Oklahoma State University Oklahoma State University CHEM 6420CHEM 6420

Fall 2007Fall 2007

Nanotechnology in Cancer Nanotechnology in Cancer TreatmentTreatment

Fundamentals of Nanotechnology: From Synthesis to Self-AssemblyFundamentals of Nanotechnology: From Synthesis to Self-Assembly

Background and Introduction Cancer

Development of abnormal cells that divide uncontrollably which have the ability to infiltrate and destroy normal body tissue 1

Chemotherapy

Nonspecificity Toxicity Adverse side effects Poor solubility

Use of anti-cancer (cytotoxic) drugs to destroy cancer cells.

Work by disrupting the growth of cancer cells 2

interdisciplinary research, cutting across the disciplines of 3

Biology Chemistry Engineering Physics Medicine

Cancer Nanotechnology

Semiconductor quantum dots (QDs) Ion oxide nanocrystals Carbon nanotubes Polymeric nanoparticles

Structural Optical Magnetic

Nanoparticles such as

Unique Properties

Molecular Cancer Imaging (QDs)

Tumor Targeting and Imaging

size-tunable optical properties of ZnS-capped CdSe QDs

Emission wavelengths are size tunable (2 nm-7 nm) 4

High molar extinction coefficients

Conjugation with copolymer improves biocompatibility, selectivity and decrease cellular toxicity 5

Correlated Optical and X-Ray Imaging

High resolution sensitivity in detection of small tumors 6

x-rays provides detailed anatomical locations

Polymer-encapsulated QDs

No chemical or enzymatic degradations

QDs cleared from the body by slow filtration or excretion out of the body

Early Cancer Detection Early cancer detection by carbon nanotubes

Nanowires

Metallic , semiconductor or polymer composite nanowires functionalized by ligands such as antibodies and oligonucleotides

capturing the targeted molecules the Nanowires changes the conductivity 8

Detect up to 10 X 10-15

concentrations

Oligonucleotide modified carbon nanotubes as the high-resolution atomic force microscopy tips to determine targeted DNA sequences

can detect change in single base mismatch in a kilobase size DNA strains 7

Targeted Cancer Therapy Active targeting

Conjugating the nanoparticle to the targeted organ, tumor or individual cells for preferential accumulation 9

dendrimers are synthetic, spherical, highly branched and monodispersed macromolecules

Biodegradable polyester dendrimers

Intracellular release of drug component

Tunable architectures and molecular weights to leads to optimize tumor accumulation and drug delivery.

Polyester dendrimer based on 2,2-bis(hydroxymethyl)propionic acid

Designed by encapsulating, covalently attaching or adsorbing therapeutic and diagnostic agents to the nanoparticle 10

Recently Food and Drug Administration (FDA) approved AbraxaneTM an albumin-paclitaxel (TaxolTM) nanoparticle drug for the breast cancer treatment. Nanoparticle structure was designed by linking hydrophobic cancer drug (Taxol) and tumor-targeting ligand to hydrophilic and biodegradable polymer.

Delivers 50% higher dose of active agent TaxolTM to the targeted tumor areas.

Nanoparticle Drugs

The first major direction in design and development of nanoparticles are monofunctional, dual functional, tri functional and multiple functional probes.

Bioconjugated QDs with both targeting and imaging functions will be useful in targeted tumor imaging and molecular profiling applications.

Consequently nanoparticles with three functional groups could be designed for simultaneous imaging and therapy with targeting.

The second direction is to study nanoparticle distribution, metabolism, excretion and pharmacodynamics in in vivo animal modals. These investigations will be very impotent in the development and design of nanoparticles for clinical applications in cancer treatment.

Feature Directions

Reference

1) Hahn, W. C.; Weinberg, R. A. Nat. Rev. Cancer, 2002, 2, 331–341.2) Liotta, L.; Petricoin, E. Nat. Rev Genet, 2000, 1, 48–56. 3) Henglein, A.; Chem. Rev. 1989, 89, 1861–1873.4) Alivisatos, P.; Nat. Biotechnol, 2004, 22, 47–52. 5) Alivisatos, A .P.; Gu, W. W.; Annu. Rev. Biomed. Eng. 2005, 7, 55–76.6) Golub, T .R.; Slonim, D. K.; Tamayo, P.; Huard, C.; Gaasenbeek, M.; Science, 1999, 286, 531–537. 7) Woolley, A. T.; Guillemette, C.; Cheung, C. L.; Housman, D. E.; Lieber, C. M.; Nat.Biotechnol, 2000, 18, 760–763. 8) Hahm, J.; Lieber, C. M.; Nano Lett, 2004, 4, 51–54. 9) Patri, A. K.; Curr. Opin. Chem. Biol, 2002, 6, 466-468.10) Andresen, T. L.; Prog. Lipid Res, 2005, 44, 68-72.