Nanostructures show potential to aid in the diagnosis and treatment of pediatric brain cancer

Chemistry meets biology in this innovative research program. Using synthetic particles invisible to the naked eye, researchers hope to better diagnose and treat childhood brain cancer, the third most common cancer of children. The particles are called nanostructures or nanoparticles because they are measured in nanometers, an almost unimaginably small unit, a billion times shorter than a yardstick.

The magnified nanoparticles shown here are actually about 1,000 times smaller than the width of a human hair.
The magnified nanoparticles shown here are actually about 1,000 times smaller than the width of a human hair.

“Nanoscience and nanotechnology have been on the rise for a decade, and they are at the point now where they can have an impact beyond general science,” says Karen L. Wooley, Ph.D., who is leading this program to take advantage of nanoparticles in the fight against astrocytomas, cancers of the star-shaped support cells of the brain.

Astrocytomas make up about 40 percent of brain tumors in children. Childhood brain cancer is especially devastating because the developing brain is so sensitive to radiation, often used to treat cancer. Surgery to remove brain tumors is not always successful because the tumor’s edges are hard to see, and furthermore, surgery is often avoided because of the danger of brain damage. By keeping out medications used against cancer, the blood-brain barrier adds yet another obstacle to treatment.

“The high-grade form of this cancer has an especially poor prognosis,” Wooley says. “And in the past two decades research hasn’t been able to make much of an improvement in survival. So this is a significant challenge, but one that’s critically important.”

In Wooley’s chemistry laboratory researchers invented novel polymers with non-stick properties. “We originally invented these polymers for the Navy to coat ships and inhibit marine organisms from settling on the hull,” Wooley explains. “Now we’ve found a way to make these coatings into really small particulates, or nanostructures, so they can circulate in the body.”

Think of these nanoparticles as tiny packages with internal compartments that can hold medicines and at the same time carry substances that can be scanned with medical imaging devices. The outside of the nanoparticles can be designed with “hooks” to bind them to cancer cells. The researchers expect that these “multitasking” nanoparticles will be able to highlight cancer cells and monitor the disease while the cancer-fighting drugs within them attack the cells. By playing with the size and composition of the nanoparticles, the researchers hope to enable the particles to slip across the blood-brain barrier.

“The Children’s Discovery Institute provided seed funds to get us together and get us working,” Wooley says. “And now we have to run with it and make substantial progress in a brief period of time. We’re working very aggressively on the project.”

Wooley, the James S. McDonnell Distinguished University Professor in Arts & Sciences in the chemistry department, is joined in this venture by researchers led by John-Stephen A. Taylor, Ph.D., professor of chemistry, Sheila A. Stewart, Ph.D., assistant professor of cell biology and physiology, and Jeffrey R. Leonard, M.D., assistant professor of neurosurgery and a neurosurgeon with St. Louis Children’s Hospital.

Each of these laboratories has a vital role in the program’s success: The Taylor lab will develop the molecular recognition sequences that allow the nanoparticles to dock on cancer cells; the Stewart lab will manipulate experimental cells so that they have surface components that can be recognized and targeted by the nanostructures as a way to test the particles’ effectiveness; and the Leonard lab will bring both expertise in pediatric brain cancer and animal models that can duplicate the disease to confirm how well the particles work in living organisms.

“Things become exciting when people from different disciplines get together,” Wooley says. “Our different backgrounds bring new perspectives. In talking with John, Sheila and Jeff, it became clear that together we could create technology that would be far advanced in the ability to detect and treat pediatric brain cancers.”