Fighting Cancer from the Inside Out

Manmade molecules that deliver drugs directly to cancer cells, tiny sensors that monitor oxygen levels in the bloodstream, molecular surgery to remove defective genes - it all sounds like science fiction. But technology to make these advances possible is being developed today by scientists at the Michigan Nanotechnology Institute for Medicine and the Biological Sciences (M-NIMBS).

"Nanotechnology allows us to make materials that are thousands of times smaller than the smallest cell in the body," says James R. Baker Jr., M.D., Ruth Dow Doan Professor of Biologic Nanotechnology at the University of Michigan, who directs the Michigan Nanotechnology Institute. "Because these materials are so small, they can easily get inside cells and change how they work."So how small is small?

One nanometer equals one-billionth of a meter, which means it would take about 80,000 nanometers lined up side-by-side to equal the diameter of a human hair. "To compare the size of a nanoparticle to the size of a typical cell, think of a grain of sand on a football field," Baker says.

When it comes to fighting cancer, scientists are excited about developing new nanotechnology-based treatments that will be more effective and have fewer side-effects than traditional therapies. As an example, Baker points to the recent creation, by M-NIMBS scientists, of what he calls the "nanotechnology equivalent of a Trojan horse."

It's a manmade nanoparticle called a dendrimer designed to smuggle a powerful anti-cancer drug inside tumor cells - increasing the drug's cancer-killing activity and reducing its toxic side effects. Less than five nanometers in diameter, the particle is small enough to slip through tiny openings in cell membranes.

Dendrimers have a tree-like structure with many branches where scientists can attach drugs and molecules. U-M scientists attached methotrexate, a powerful anticancer drug, to one branch of the dendrimer. On another branch, they attached their secret ingredient - a vitamin called folic acid.

Folic acid, or folate, is an important vitamin required for the healthy functioning of all cells. But cancer cells, in particular, seem to need more than average amounts.

By taking advantage of a cancer cell's appetite for folate, U-M scientists were able to concentrate more of the toxic drug in cancer cells, while reducing side-effects on normal cells.

"It's like a Trojan horse," Baker explains. "The cancer cell thinks it's bringing in food. Once inside, however, there's a poison on the nanoparticle that kills the cell.

When Baker and his research team gave the nanoparticle-methotrexate combination to mice with tumors, they found it was more effective than giving the cancer-killing drug alone.

"Effectively, we delayed the growth of tumors in mice for 30 days," Baker says. "That is significant, when you consider that one month for a mouse is the equivalent of about three years for a person."

Although still in the experimental stage, Baker is very positive about nanotechnology's potential to fundamentally change the way physicians treat cancer.

"Instead of trying to kill the cancer, we could treat it as a chronic disease, like diabetes, and suppress it," he explains. "Using a nanotechnology-based therapy would keep the cancer from growing and allow the patient to live a normal life without ever having to remove the cancer."

Researchers at the Michigan Nanotechnology Institute also are exploring the use of nanotechnology-based therapies using other anti-cancer drugs.

"There are many drugs that are very effective, but they can't be used now because they are too toxic," Baker says. "If these drugs can be delivered with a targeted nanoparticle system, we may be able to overcome the toxicity problem and provide a broader range of therapeutic agents for people with cancer."

The research was funded by the National Cancer Institute. The U-M has filed a patent application on targeted nanoparticle technology. Avidimer Therapeutics, a biopharmaceutical company in Ann Arbor, holds licensing rights to this technology. Baker has a significant financial interest in the company.

For more information about nanotechnology, visit these Web sites:

Michigan Nanotechnology Institute for Medicine and Biological Sciences http://www.nano.med.umich.edu/

National Nanotechnology Initiativehttp://www.nano.gov

National Cancer Institute Alliance for Nanotechnology in Cancerhttp://nano.cancer.gov/

A targeted newswire featuring breaking medical news stories from over 200 leading academic and research institutions including: Johns Hopkins, Stanford, Harvard, and the Mayo Clinic.