Amila'A'Dissanayake

1
Nanotechnology in Cancer Treatment
Fundamentals of Nanotechnology From Synthesis to
Self-Assembly

• 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, 331341. 2) Liotta, L. Petricoin, E.
Nat. Rev Genet, 2000, 1, 4856. 3) Henglein, A.
Chem. Rev. 1989, 89, 18611873. 4) Alivisatos,
P. Nat. Biotechnol, 2004, 22, 4752. 5)
Alivisatos, A .P. Gu, W. W. Annu. Rev. Biomed.
Eng. 2005, 7, 5576. 6) Golub, T .R. Slonim, D.
K. Tamayo, P. Huard, C. Gaasenbeek, M.
Science, 1999, 286, 531537. 7) Woolley, A. T.
Guillemette, C. Cheung, C. L. Housman, D. E.
Lieber, C. M. Nat.Biotechnol, 2000, 18, 760763.
8) Hahm, J. Lieber, C. M. Nano Lett, 2004, 4,
5154. 9) Patri, A. K. Curr. Opin. Chem. Biol,
2002, 6, 466-468. 10) Andresen, T. L. Prog.
Lipid Res, 2005, 44, 68-72.