Post on 31-Dec-2015
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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.