Treating brain tumors is traditionally difficult because of the blood-brain barrier, which prevents harmful substances from traveling through the bloodstream into the brain. In order for chemotherapy to treat a tumor, it must penetrate this barrier.
'Thinking outside the box is a must for developing brain cancer treatments. Drugs don't get into the brain when delivered in the normal way, which explains in part why some current treatments for brain tumors are generally not effective. Targeting the tumor vasculature with nanoparticles containing a payload will overcome these issues,' says study author Alnawaz Rehemtulla, Ph.D., professor of radiology and radiation oncology at the U-M Medical School and professor of environmental health sciences at the School of Public Health.
Researchers tested the nanoparticles in cell cultures and animal models. The studies showed that nanoparticles traveled to the tumor, resulting in less Photofrin exposure throughout the body and enhanced exposure within the tumor. This allowed a larger window for activating the drug with light. It would also eliminate a common side effect of photodynamic therapy, in which healthy skin becomes sensitive to light.
In rat studies, researchers found those treated traditionally with Photofrin survived 13 days, while rats treated with Photofrin incorporated into a nanoparticle survived an average of 33 days. Forty percent of the rats remained disease-free six months after treatment.
The researchers also found twice the amount of the contrast agent at the tumor site when using targeted nanoparticles, suggesting the nanoparticles were attracted to the tumor site.
The advantage of this delivery system is the ability to attack the tumor with higher doses of a drug while sparing normal tissue from a drug's toxic side effects.
'Our research suggests that you can take a drug that may be toxic to normal tissue - it could be any type of drug, not just photodynamic - and you could deliver higher doses of that drug for a more powerful punch,' says Rehemtulla.
If nanoparticle delivery proves to be safe in humans, it will allow researchers to re-examine previously developed drugs that had to be discarded because they caused too many dangerous side effects in patients.
By combining the drug with a contrast agent, researchers were able using imaging techniques to determine whether the drug actually got to the tumor. This technique could have potential to diagnosis brain tumors early, as well as to help researchers determine when to deliver a drug or when to administer the next dose.
Further lab research is necessary before clinical trials of nanoparticle technology can be undertaken. It has been estimated that more than 18,800 people will be diagnosed with brain cancer this year, and 12,820 will die from it.