RESEARCH, SCHOLARSHIP AND CREATIVE ACTIVITY AT THE UNIVERSITY OF LOUISVILLE FALL 2006

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Cancer Hunters

In Hollywood’s 1966 sci-fi opus, Fantastic Voyage, doctors inside a submarine were miniaturized, injected into a patient’s bloodstream and propelled into his brain to fix a blood clot.

Today, researchers at U of L and elsewhere hope to do similar medical procedures—but without the need to shrink doctors. Instead they want to inject into the blood human-made nanoparticles—thousands of times smaller than blood cells—that target and destroy diseased cells.

Kyung Kang, professor of chemical engineering in the Speed School, is studying the use of special nanoparticles that can both detect and shrink breast tumors.

Kang’s interest in nanoparticles that target breast cancer began when she realized the limitations of optical mammography, which uses light instead of X-rays to detect breast tumors.

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"Optical mammography is good unless the tumor is situated deep," Kang says. "That’s when you need an optical contrast agent."

Kang began to study the idea of using nanoparticles coated with a gold layer as well as a substance known as a fluorophore that would make tumors shine and be detectable by imaging devices.

At the same time, she examined the idea of using the nanoparticles to kill the tumor cells once they reached them.

Kang is working to perfect these nanoparticles in collaboration with Dr. Sham Kakar, an associate professor of medicine at U of L and a tumor biologist who works at U of L’s James Graham Brown Cancer Center. Also on the research team are chemical engineering Ph.D. students Bin Hong and Hanzhu Jin.

Approaches differ on using nanoparticles to detect and treat cancer. Some researchers elsewhere use a combination of nanoparticles and light to zap tumors. Kang and Kakar use tumor-targeted nanoparticles in tandem with magnetism to heat and shrink tumors.

Once the magnetic nanoparticles seek and cling to cancer cells they are heated by a magnetic field that penetrates the body. The field is generated by an induction heater and directed by a small applicator held above the skin at the tumor site.

The heat generated in the nanoparticle heats the cancer cells and disables enzymes needed for cancer growth.

"Our body temperature is 36 degrees centrigrade, but we only need to heat up the nanoparticles to about 45 degrees centigrade [about 113 degrees Fahrenheit] to deactivate the enzyme and slowly shrink the tumor," Kang says. "You only need to heat it a little, not cook it."

Because the treatment targets cancer cells only, damage to surrounding normal tissue is minimized—unlike chemotherapy or radiation treatments.

The nanoparticles can find and bind to the tumor cells because they are tagged with a ligand called LHRH that seeks and binds to a specific receptor found in cancer cells.

"Once we bind LHRH to these magnetic particles they go to the tumor cell, bind on the surface and get internalized in the cell," Kakar says. "Then we apply the magnetic field, heat the cell and kill it."

Kang has been using a pancake-shaped 1-inch diametic applicator which she says best directs the magnetic field to the nanoparticles, minimizing heat damage to normal tissues. Multiple treatments of a few minutes each appear to shrink the tumors.

"We apply the magnetic field only for 15 minutes, then we look at the cells under a microscope to see if they changed," Kakar says. "After heat application we are killing 95 to 100 percent of the cells."

More studies are under way to coat the nanoparticles with different substances to improve their detection and targeting, as well as to gauge any possible side effects. The scientists also want to study piggybacking chemicals to nanoparticles for more targeted chemotherapy.

So far, the researchers have tested the technique only in lab tissue cultures but are embarking on tests in lab animals. Human trials could follow at an undetermined time.

"The positive thing about this type of therapy is that it is minimally invasive and painless," Kang says.

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