Nanotechnology in Cancer Treatment

1. Fundamentals of Nanotechnology: From Synthesis to Self-Assembly Nanotechnology in Cancer Treatment Amila.A.Dissanayake Department of Chemistry Oklahoma State University CHEM 6420 Fall 2007

2. Background and Introduction • Cancer Development of abnormal cells that divide uncontrollably which have the ability to infiltrate and destroy normal body tissue 1 • Chemotherapy Use of anti-cancer (cytotoxic) drugs to destroy cancer cells. Work by disrupting the growth of cancer cells 2 • Nonspecificity • Toxicity • Adverse side effects • Poor solubility

3. Cancer Nanotechnology • interdisciplinary research, cutting across the disciplines of 3 • Biology • Chemistry • Engineering • Physics • Medicine Nanoparticles such as • Semiconductor quantum dots (QDs) • Ion oxide nanocrystals • Carbon nanotubes • Polymeric nanoparticles Unique Properties • Structural • Optical • Magnetic

4. Molecular Cancer Imaging (QDs) • Tumor Targeting and Imaging 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 size-tunable optical properties of ZnS-capped CdSe QDs

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

6. Early Cancer Detection • Early cancer detection by carbon nanotubes 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 • 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

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

8. Nanoparticle Drugs • 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.

9. Feature Directions • 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.

10. 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.