Nanotechnology in Cancer Treatment and Detection

Richard Acosta

Motivation • Ineffectiveness of many Cancer treatments

• Numerous side effects

• Difficulties in early Cancer detection

• No immunization

Scale and Scope 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

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

• 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

Nanoparticle Specialization

Uses in Treatment 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

Amount of weight loss and white blood cell count confirmed far lower toxicity for the targeted nanoparticles

Comparative efficacy study in LNCaP s.c. xenograft nude mouse model of PCa

Farokhzad O. C. et.al. PNAS 2006;103:6315-6320

©2006 by National Academy of Sciences

Uses in Treatment Photothermal Ablation

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

Uses in Detection Fluorescent Microscopy

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