Doctors diagnose more than 22,000 new cases of malignant glioma, or brain tumors, in the United States each year. Despite modern methods of surgery, chemotherapy, and radiation, median survival rate is about one year, and the tumor almost always grows back after treatment.
Faced with these grim statistics, scientists continue to look for better treatment options. Surgery to remove a malignant brain tumor is often difficult because tumor cells can spread into crucial areas of the brain beyond the primary area. Traditional chemotherapy is inefficient because the blood-brain barrier prevents many molecules from getting to the tumor cells in the brain.
One method that shows promise is a technique called convection enhanced delivery (CED) to infuse chemotherapy drugs into the brain through a catheter, using hydrostatic pressure to deliver the medicine directly to the tumor. But early clinical trials using CED to treat brain tumors have shown that it’s difficult to get the drugs to where they’re supposed to go. It’s essentially a blind procedure, and sometimes the therapeutics just get absorbed into the fluids around the brain and washed away.To give physicians greater visibility, neurosurgeon Bakthiar Yamini, MD, and his colleagues at the University of Chicago are working with a new technology that uses microscopic particles that can be tracked by MRI to carry chemotherapy drugs. Such a process would enable physicians to monitor treatments to make sure the drugs are reaching their destination.
Yamini said these nanoparticles would allow physicians to adjust treatments in real time.
“You could see where the delivery is going, and if it’s not going to exactly where you want, then you could adjust your catheter,” he said. “It’s real-time image guidance.”
The nanoparticles are made by a Nebraska-based company called LNKChemsolutions using FDA-approved polymers to create a shell that carries the chemotherapy drug. The shell contains flecks of iron oxide that show up on the MRI scans, so doctors can track them from the injection site to the target area. The polymers and iron oxide break down over a month or so, and in animal models they have been able to distribute chemotherapy drugs efficiently with no additional toxicity.
More importantly, in a study published recently in the journal Nanomedicine, Yamini and his colleagues showed that nanoparticles carrying a commonly-used chemotherapy drug called temozolomide reduced the size of tumors and extended survival in the animal models.
Yamini said one of the challenges with this method is getting the right amount of drug to the tumor cells, especially the ones that have spread out from the primary tumor.
“Just because you can cover it with your imaging doesn’t mean necessarily that the tumor cell is getting the therapeutic agent,” he said.He and his team are also working on a more advanced, targeted approach to make sure the nanoparticles do get to their destination. In this case, a ligand, which is a molecule that binds to a site on a target protein, is added to the nanoparticles to help it bind to the tumor cells. But finding the right target can be tricky.
“One of the big problems with brain tumors is there’s no clear target,” Yamini said. “Some of the targets they express are also expressed on normal cells, and then some targets that are there, not all the tumor cells have them.”
Despite these challenges, Yamini thinks nanoparticles that can be tracked with imaging could be used for treating other diseases some day.
“It’s really a platform, a multifunctional platform,” he said. “Any disease you could imagine that has a specific cell that’s pathological, then you can target that cell with the therapeutic that’s appropriate for that disease.”
Bernal G.M., LaRiviere M.J., Mansour N., Pytel P., Cahill K.E., Voce D.J., Kang S., Spretz R., Welp U. & Noriega S.E. & (2013). Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma, Nanomedicine: Nanotechnology, Biology and Medicine, DOI: 10.1016/j.nano.2013.07.003