Novel Treatment for Deadly Brain Tumors Combines Nanoparticles, Microbubbles and Focused Ultrasound

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Richard J. Price, Ph.D. is investigating a novel combination of nanoparticles, microbubbles and focused ultrasound – a combination that he believes could effectively treat and possibly cure diseases of the central nervous system, including brain tumors, dementia and Parkinson’s disease.

Price is Associate Professor of Biomedical Engineering at the University of Virginia and Research Director of UVA’s Focused Ultrasound Center. He has received a $100,000 research award from the Focused Ultrasound Surgery Foundation to study whether nanoparticles, in combination with microbubbles the size of a red blood cell, can actually deliver targeted therapies across the tight blood brain barrier (BBB) to kill glioblastoma multiforme tumors when oscillated with a focused ultrasound beam. Highly aggressive and deadly, glioblastomas, or GBMs, are the most common form of primary brain cancer and have an extremely poor prognosis.

Besides surmounting the daunting technical challenges of delivering drugs across the BBB, Price’s approach will use smaller doses of chemotherapy and deliver higher concentrations of drugs to tumors than current cancer therapies. For patients, the new treatment could mean less systemic toxicity, fewer side effects and more effective therapy.

“I’m thrilled about the award. It’s a critical piece of funding for our research,” Price said. “Without this support, we would be at a roadblock right now and not able to move this research to where we want it to be. It’s like the kindling wood to get the fire started.”

Plenty of experts are studying how to get drugs across the blood brain barrier (BBB). Its tight endothelial (cell wall) junctions control what molecules move in and out of the brain. The mechanisms through which ultrasound and microbubbles open the BBB are not fully understood. But Price has a novel application that takes advantage of this phenomenon. He is trying to use ultrasound waves to drive solid nanoparticles comprised of biodegradable polymers through pores in blood vessel walls. The nanoparticles will be a platform of sorts on which to load different types of therapies, depending on the type of tumor. These therapies can include various cancer drugs, genes, even silencing RNA. But, when combined with microbubbles, ultrasound waves can rip blood vessels apart. So, safely opening the blood brain barrier is a major hurdle.

“In this research, we hope to define what the safety parameters are for a given ultrasound frequency,” Price said. “How much power can you apply and keep the opening of the blood brain barrier safe? If you’re treating a region of the brain that may have tumor cells, but also normal neurons, you need to be careful.”

If Price’s research pans out, a few years from now it may be possible to map out a brain tumor in 3-D, then tailor the approach for focused ultrasound-mediated drug delivery depending on the position of the tumor.

“If the studies in this proposal are successful, the next step will be to answer the question of drug loading, specifically how many nanoparticles can we safely get across the BBB?” Price explained. “And we’ll need more information before we can address that question.”

His work with a nanoparticle platform can also have broad implications in treating other diseases of the central nervous system. Price believes nanoparticles could be perfect delivery systems for drugs to treat Parkinson’s disease. “There are dozens of other diseases this research may help long term,” Price said.

Written by Ellen C., McKenna