Nanotechnology in Cancer Treatment and Detection

Nanotechnology in Cancer Treatment and Detection
Richard Acosta

Motivation
• Ineffectiveness of many Cancer treatments
• Numerous side effects
• Difficulties in early Cancer detection
• No immunization

The nanoparticles discussed in
this presentation are typically
between 20-150 nm or roughly
100 times smaller than most
human cells
Cancer Nanotechnology research
is interdisciplinary and
incorporates Biology, Chemistry,
Engineering, Medicine, and
Physics
Scale and Scope

Properties of Cancer Cells
• Epidermal Growth Factor Receptor (EGFR)
over expression and over activity
have been associated many different
types of Cancer
• Cancer cells have a unique properties that can be exploited by nanoparticles
• Their rapid rate of growth causes them to intake an abnormal amount of
nutrients (i.e., folic acid)
• Nanoparticles can be used to target bio-markers or antigens that are
highly specific to Cancer cells

Nanoparticle Specialization
• 99% of chemotherapy drugs do not reach the
Cancer cells
• Nanotubes, nanorods, dendrimers,
nanospheres, nanoantennas, … using
carbon, iron, gadolinium, gold, silicon, etc.
• Antigen binding peptide ligands are attached
to the nanostructures
• Folic acid baiting
• Passive targeting - Leaky blood vessels near
tumors cause the nanoparticles to cluster
around the tumors

Intracellular Drug Delivery
The Trojan Horse
Cytotoxic chemical payload
Methotrexate, Docetaxel, etc…
Uses in Treatment

Experiment on mice bearing
human prostate tumors
After approximately 3 months
100% of the mice treated with the
targeted nanoparticles survived
57% of the mice treated with
untargeted nanoparticles survived
14% of the mice with Docetaxel
alone survived
Uses in Treatment
Amount of weight loss and white
blood cell count confirmed far lower
toxicity for the targeted nanoparticles

©2006 by National Academy of Sciences
Comparative efficacy study in LNCaP s.c. xenograft nude mouse model of PCa
Farokhzad O. C. et.al. PNAS 2006;103:6315-6320

Photothermal Ablation
Uses in Treatment
Cancer cells die at 42° C (108° F), normal cells die at about 46° C (115° F)
Current optical fiber treatment
Hollow, gold nanospheres are 50 times more effective at absorbing light near the
infrared than solid gold nanoparticles
Nanoparticles can be tuned to be excited only by certain ranges of light

Uses in Treatment
In another study, pre-clinical trials reveal that a single intravenous nanoparticle
injection eradicated 100 percent of tumors in mice when exposed to
near-infrared light.
Most work is being done with near-infrared light, which is harmless to humans but
can only penetrate human tissue about 1.5 inches. Nanoparticles heated up
to 70° C (160° F)
The Kanzius RF Machine uses radio waves for dielectric heating

Uses in Detection
Gold nanoparticles in this image showed 600 percent more affinity to Cancer
cells than healthy cells (EGFR binding)
White light and simple, inexpensive microscope is all that’s necessary for
powerful ex vivo Cancer detection.
The scattering is so strong that even one nanoparticle can be detected.

Uses in Detection
Using a metal-organic framework with metals such as gadolinium or iron,
nanoparticles can be used as MRI contrast agents
For the same amount of contrast, only 1/3 of the contrast agent is necessary
using nanoparticle targeting

Fluorescent Microscopy
Uses in Detection
Nanoparticles can serve as dual detection devices for both magnetic
resonance and microscopy

Current Limitations
Cancer targeting is highly dependent on surface chemistry. Not just any
nanoparticle will work.
The need for biocompatible and stable nanoparticles
Side-effects and toxicity
Environmental impact
Uncharted territory

Future
Human clinical trials within the next 2-3 years
Highly specific team of communicating multifunctional nanoparticles used
in the discovery, treatment, and prevention of Cancer growth
Safer, more consistent, and highly specific nanoparticle production
Turning Cancer into a chronic, but manageable disease within the next
15-20 years

Summary
-Different types of Cancer cells have unique properties that can be
exploited by nanoparticles to target the Cancer cells
-Nanoparticles can be used to detect/monitor (by utilizing or adding optic,
magnetic, and fluorescent properties) and to treat Cancer (by Heat ablation,
chemotherapy, gene therapy).
-No human trials have been performed yet and human trials are still at
least a few years away. (Unknown side effects, toxicity, difficulty in
manufacturing and harmful byproducts, need for highly specific
nanoparticles)

Sources
• University of California - Santa Cruz (2009, March 28). Hollow Gold Nanospheres Show Promise For Biomedical And Other
Applications. ScienceDaily. Retrieved May 24, 2009, from http://www.sciencedaily.com- /releases/2009/03/090322154415.htm
• University of Texas M. D. Anderson Cancer Center (2009, February 8). Targeted Nanospheres Find, Penetrate, Then Fuel
Burning Of Melanoma. ScienceDaily. Retrieved May 24, 2009,
from http://www.sciencedaily.com- /releases/2009/02/090202074856.htm
• Couvreur P, Vauthier C. Nanotechnology: intelligent design to treat complex disease. Pharmaceutical
Research. 2006; 23(7): 1417-50.
• Sunderland CJ, Steiert M, Talmadge JE, Derfus AM, Barry SE. Targeted nanoparticles for
detecting and treating cancer. Drug Development Research. 2006; 67: 70-93.
• Yih TC, Al-Fandi M. Engineered nanoparticles as precise drug delivery systems. Journal of Cellular
Biochemistry. 2006; 97: 1184-90.
• El-Sayed, Mostafa. Gold Nanoparticles May Simplify Cancer Detection. Georgia Institute of Technology. 2005
• Misty D. Rowe, Douglas H. Thamm, Susan L. Kraft, Stephen G. Boyes. Polymer-Modified Gadolinium Metal-Organic Framework
Nanoparticles Used as Multifunctional Nanomedicines for the Targeted Imaging and Treatment of Cancer.
Biomacromolecules 2009 10 (4), 983-993
• Chungang Wang, Jiji Chen, Tom Talavage, Joseph Irudayaraj. Gold Nanorod/Fe3O4 Nanoparticle Nano-Pearl-Necklaces for
Simultaneous Targeting, Dual-Mode Imaging, and Photothermal Ablation of Cancer Cells. Angewandte
Chemie International Edition (2009)
• L. Denton, Michael S. Foltz, Gary D. Noojin, Larry E. Estlack, Robert J. Thomas, and Benjamin A. Rockwell. Determination of
threshold average temperature for cell death in an in vitro retinal model using thermograph Proc. SPIE 7175,
71750G (2009), DOI:10.1117/12.807861
• Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo PNAS 2006 103:6315-6320; published online
before print April 10, 2006, doi:10.1073/pnas.0601755103
• http://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor
• http://en.wikipedia.org/wiki/Nanomedicine
• http://en.wikipedia.org/wiki/Surface_plasmon_resonance
• http://en.wikipedia.org/wiki/Fluorescence_microscopy
• http://en.wikipedia.org/wiki/Methotrexate
• http://en.wikipedia.org/wiki/Docetaxel

Questions
1) Which of the following are not potential methods for treating Cancer
using nanotechnology.
a) Photothermal ablation
b) Folic acid introduction
c) Cytotoxic drug delivery
d) Gene therapy
e) None of the above
2) A cause for the stall in utilizing nanotechnology treatment on a mass scale is
a) Unknown toxic effects of nanoparticles
b) Environmental repercussions
c) Lack of human clinical trials
d) Inefficient nanoparticle creation techniques
e) All of the above