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Tiny Particles Pack Powerful Punch

Network - Spring 2007

By Scott Merville

Nanoparticles — molecules so small that they are measured in billionths of a meter — have a talent for gathering inside tumors.

After slipping through large pores in leaky blood vessels that nourish tumors, these tiny materials can be taken up into the cancer cells. Their potential to destroy tumors is being tested by M. D. Anderson researchers, who are investigating the use of nanoparticles to deliver therapy, imaging agents or both.

“Nanoparticles can be used for both therapy and diagnostics,” says Chun Li, Ph.D., professor in the Department of Experimental Diagnostic Imaging. Combining the two functions in one nanoparticle would allow “you to watch where the therapy goes and monitor the treatment in real time.” Li is developing such a particle.

With a $2.5 million, five-year National Cancer Institute Nanotechnology Platform Partnerships program grant, Li also is working with Eastman Kodak to develop nanoparticles that bind to tumors and light up under near-infrared light. Near-infrared fluorescence-based optical imaging is sensitive, involves no ionizing radiation and allows real-time visualization, he says.

Li has connected molecules of the drug paclitaxel to a nano-sized, water-soluble polymer, which appears to heighten the chemotherapy’s effect. Polymers are molecules that consist of repeated structural units. That combination is being tested in a Phase III lung cancer clinical trial sponsored by Cell Therapeutics, Inc.

Nanoparticles, researchers say, will work best with a targeting component that binds to cancer cells and avoids normal tissue.

Hitching a ride

Michael Rosenblum, Ph.D., professor in the Department of Experimental Therapeutics, specializes in targeting constructs — antibodies, growth factors, peptides — that home in on cancer.

He has three drugs in development, which combine a targeting component with a cancer toxin. While these fusion proteins are not nanoparticles, Rosenblum is collaborating with colleagues from Rice University to examine the potential role of fullerenes in a fusion approach. Also called buckyballs, fullerenes are nanospheres of 60 carbon atoms.

The researchers reported last year that buckyballs can carry chemotherapeutic agents such as Taxol. They also showed a single antibody that targets skin cancer is capable of carrying up to 40 buckyballs, which did not hinder the antibody’s cancer-targeting ability. The findings raise the possibility of developing powerful, tightly targeted therapeutics by attaching buckyballs loaded with drugs to an antibody or other targeting molecule, Rosenblum says.

As good as gold

With its low toxicity and well-known optical, biological and biodistribution properties, gold is an attractive nanomaterial, says John D. Hazle, Ph.D., chair of the Department of Imaging Physics.

Hazle collaborates with researchers at Rice, who invented gold nanoshells, and Nanospectra Biosciences to exploit the unique optical properties of nanoshells in oncology. When exposed to near-infrared light, they become intensely hot and burn the tumor cells or microvasculature, Hazle says.

Renata Pasqualini, Ph.D., and Wadih Arap, M.D., Ph.D., both professors of medicine in the Departments of Genitourinary Medical Oncology and Cancer Biology, are harnessing gold to viral particles, creating a “nanoshuttle” to target tumors. The viral particles are engineered to zero in on the target tissue’s vascular “zip code.” Earlier, they discovered that the human vascular system has unique molecular addresses for different organs and tissues.

In a laboratory study, they found that targeted viral and gold nanoparticles could be “tuned” to destroy tissue or emit signals detected by imaging devices. The system can be adapted to carry drugs, genes or restorative stem cells.

These are only a few of the ways nanoparticles are being studied as
M. D. Anderson works collaboratively with various Houston-based institutions to discover how they can deliver therapy, help with diagnosis, be eliminated after they deliver their payload and be used to silence cancer-promoting genes.

© 2015 The University of Texas MD Anderson Cancer Center