THE SEARCH FOR A KINDER, GENTLER CHEMOTHERAPY
09 September 2004 - Georgia Institute of Technology

Painful and damaging chemotherapy may one day be a thing of the past. Researchers at the Georgia Institute of Technology and Purdue University have developed nano-sized particles that can target and trick cancer cells into absorbing them. Once inside, the particles may soon be able to deliver a pharmaceutical payload, killing the tumor from within and avoiding the destruction of healthy cells responsible for much of the damage caused by traditional chemotherapy. The research is published in the August 25 edition of the Journal of the American Chemical Society.

"We've developed a class of particles called core/shell nanogels that we can functionalize with a specific kind of chemistry that allows them to target cancer cells," said L. Andrew Lyon, associate professor at Georgia Tech's School of Chemistry and Biochemistry.

That specific kind of chemistry is folic acid. Cancer cells have more receptors for folic acid and absorb more of the nutrient than healthy cells. In a process akin to hiding a dog's heartworm pill in a glob of peanut butter, researchers covered the surface of the nanogels with folic acid, disguising the particles as an essential nutrient. Once the cancer cells took the particles in, researchers increased the temperature of the cells, causing the particles to clump together and shrink, killing the cell.

Heating the cell is a crucial step in triggering the particles to destroy cells, but it's also a safeguard. Cancer cells have more folic acid receptors than normal cells, but normal cells could still absorb the nanoparticles. By applying a targeted heat source, like ultrasound, only to the tumor, doctors should be able to avoid killing healthy cells that happen to take in the nanoparticles.

"The possibility for using these nanoparticles as vehicles to target and kill only cancer cells is particularly exciting," said Jean Chmielewski, professor of chemistry at Purdue University. "Decorating the exterior of the vehicle with folic acid is a very direct route to enter cancer cells. This type of an approach will bring cancer chemotherapy to a new level of treatment," she said.

Traditional chemotherapy, by contrast, can be described as a shotgun approach with the cellular poisons affecting tumors and healthy cells alike. Nausea, vomiting, hair loss, anxiety and a reduction in red blood cells are just some of the side effects that can occur with chemotherapy.

"If there's a way to specifically target medicine to the site of disease, that makes this potential treatment all the more effective because then presumably you could use smaller doses and avoid the collateral damage that occurs during traditional chemotherapy," said Lyon.

Now that they've gotten cancer cells to take in the nanoparticles, the next step is to see how they behave with a toxic payload. "In the lab right now we're loading particles with anticancer agents and understanding the fundamentals of how the particles can encapsulate them, how tightly they can hold onto them and how closely we can regulate the uptake and release," said Lyon.

http://www.gatech.edu

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