A UH researcher is developing and testing the nanoparticle holder as a potential treatment for glioblastoma
With a survival rate of only five years, the most common and dangerous form of primary brain tumor, glioblastoma multiforme, is difficult to treat using current systems that rely on surgery, radiation, chemotherapy, and their combinations.
“Two of the major challenges in treating gliomas include the poor transfer of chemotherapy treatments across the blood-brain barrier and the unwanted side effects of these treatments on healthy tissues,” said Sherine Majd, assistant professor of biomedical engineering at the University of Houston. “To get enough medicine across the blood-brain barrier, a high dose of the drug is needed, but this introduces more toxicity into the body and can cause more problems.”
In an article published that appeared on the cover of the January issue of Advanced healthcare materialsMajd reported that a new nanotherapy that targets glioma will only treat cancer cells, providing increased efficacy and minimizing side effects.
Iron chelate known as Dp44mT (Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone) is an effective drug known to prevent tumor development but was not used against brain tumors prior to this study. The chelate works to pull the excess iron needed by the cancer cells, thus starving them.
Using evidence from the tumors themselves, Majd has developed a Dp44mT-loaded nanoparticle carrier that can be withdrawn into glioma tumors, which present multiple IL13 (interleukin) receptors. Due to the abundance of IL13 receptors, IL13 binds have been added to the FDA-approved biodegradable polymer carrier (with Dp44mT inside) so that the receptors attract the bonds, and thus receive the drug.
Before her new pregnancy, Dp44mT was administered, but it can go anywhere in the body, even where it was not intended to go.
“It’s like an untitled envelope on it. It can land anywhere, and inside it has toxins that can kill anything. Now, with targeted delivery, we put a label on the package and it goes straight to the cancer cells,” Majd said.
Aggressive brain tumors also develop high levels of multi-drug resistance making them nearly impervious to common chemotherapies such as temozolomide or doxorubicin.
“There is, therefore, an urgent need for more effective therapeutic combinations with the ability to overcome drug resistance in aggressive glioma tumors, and to kill these malignant cells without harming healthy tissues,” Majd says.
The Majd study, which tested nanotherapy in both in vivo and in vitro, is the first report on targeted delivery of Dp44mT to malignancies.