Transcript Nanotechnology in Cancer Treatment

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
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
 Cancer Nanotechnology
interdisciplinary research, cutting across the disciplines of
 Biology
 Chemistry
 Engineering
 Physics
 Medicine
Nanoparticles such as
 Semiconductor quantum dots (QDs)
 Ion oxide nanocrystals
 Carbon nanotubes
 Polymeric nanoparticles
Unique Properties
 Structural
 Optical
 Magnetic
3
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 size-tunable optical properties of ZnS-capped CdSe QDs
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
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
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
Polyester dendrimer based on 2,2-bis(hydroxymethyl)propionic acid
and drug delivery.
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.
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.
Reference
Hahn, W. C.; Weinberg, R. A. Nat. Rev. Cancer, 2002, 2, 331–341.
Liotta, L.; Petricoin, E. Nat. Rev Genet, 2000, 1, 48–56.
Henglein, A.; Chem. Rev. 1989, 89, 1861–1873.
Alivisatos, P.; Nat. Biotechnol, 2004, 22, 47–52.
Alivisatos, A .P.; Gu, W. W.; Annu. Rev. Biomed. Eng. 2005, 7, 55–76.
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.
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