Super Small Science Holds Huge Potential

New nanotechnology institute will develop and market biomedical applications

When it comes to fighting cancer, Jim Baker is positive about nanotechnology’s potential to fundamentally change the way physicians treat the disease.

Today’s doctors can replace a worn-out hip or knee — even a damaged heart or kidney. But James R. Baker Jr., M.D., sees a future in which physicians will be able to replace defective genes or proteins, and design new therapies to fight disease from inside the cell.

It’s all part of the rapidly advancing field of nanotechnology in medicine, and it’s not just for science fiction anymore.

“Nanotechnology is changing how scientists work by giving them the ability to manipulate individual atoms and molecules in biological systems,” says Baker, the U-M’s Ruth Dow Doan Professor of Biologic Nanotechnology. “We are talking about materials that are thousands of times smaller than the smallest cell in the body. Applying nanotechnology to medicine will allow us to literally re-engineer how our cells work.”

Nanotechnology deals with particles so small they can easily slip through tiny openings in cell membranes to get inside living cells. 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 width of a human hair.

This simplified computer model of the U-M “Trojan horse” nanoparticle shows the dendrimer’s branching structure and how molecules and drugs are attached.

Photo: Jolanta Kukowska-Latallo, Michigan Nanotechnology Institute for Medicine and Biological Sciences

A pioneer in the field, Baker has been researching the biological applications of nanotechnology since the mid-1990s. He directs the Michigan Nanotechnology Institute for Medicine and Biological Sciences, which was established in April 2005. The institute’s mission is to develop and market medical and biological applications of nanotechnology.

When it comes to fighting cancer, Baker is positive about nanotechnology’s potential to fundamentally change the way physicians treat the disease. As an example, he cites recent research to develop what he calls the “nanotechnology equivalent of a Trojan horse.”

It’s a manmade nanoparticle less than five nanometers in diameter 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.

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

“The cancer cell thinks it’s bringing in food,” Baker explains. “But once inside, there’s a poison on the nanoparticle that kills the cell.”

When Jolanta Kukowska-Latallo, Ph.D., a research investigator at the Nanotechnology Institute, gave the nanoparticle-methotrexate combination to mice with tumors, she found it was more effective than giving the cancer-killing drug alone.

“Effectively, we delayed the growth of tumors in mice for 30 days,” Kukowska-Latallo says. “Taking into account the length of a mouse’s life, that is significant. One month for a mouse is about three years for a person.”

The success of the Trojan horse approach led to a recent $2.5 million, five-year Cancer Nanotechnology Platform Partnership grant from the National Cancer Institute. Baker will use the NCI funding to develop a modular dendrimer nanoparticle system that can be made-to-order using different drugs and imaging agents to create personalized cancer treatments tailored to each patient.

But the news isn’t all about cancer. In June 2005, Baker learned that the Michigan Nanotechnology Institute was one of 43 institutions to receive a Grand Challenges in Global Health Initiative grant from the Bill and Melinda Gates Foundation, the Wellcome Trust and the Canadian Institutes of Health Research.

The $6.3-million Grand Challenges grant will support development and clinical testing of a nanotechnology-based vaccine delivery system. To eliminate the need for injections and refrigeration, hepatitis B vaccine will be suspended in an anti-microbial nanoemulsion that can penetrate the skin and mucous membranes, so the vaccine can be administered with a simple nasal swab.

“We believe this nanotechnology-based approach can revolutionize how vaccines are delivered and will be an important advance in the prevention of infectious diseases in developing countries,” Baker says.

The next hurdle for researchers at the Michigan Nanotechnology Institute is to see if these nanotechnology-based treatments work as well in humans as they do in animals. Baker hopes to begin early human clinical trials of the nanoparticle cancer therapy and the hepatitis B nanoemulsion vaccine within a year.

Plans are already underway to jump-start the creation of new companies to market technologies developed at the institute, Baker adds. “We want to ensure that marketable technologies are transferred to the private sector as rapidly as possible,” he says, “so they can be developed into new drugs and therapies for people who need them.”

—SFP

For more information about nanotechnology:
Michigan Nanotechnology Institute for Medicine and Biological Sciences
www.nano.med.umich.edu

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