Glioblastoma nanomedicine eradicates recurring brain cancer in mice: study

CHICAGO, Nov. 11 (Xinhua) -- A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, according to a study posted on the website of the University of Michigan (UM) on Tuesday.

Five years ago, UM researchers knew that stopping a signal that cancer cells send out, known as STAT3, to trick immune cells into granting them safe passage within the brain, the cancer cells would be exposed and the immune system could eliminate them. The problem was how to shut down that pathway with an inhibitor, a way to get past the blood-brain barrier.

A protein called human serum albumin, which is present in blood, is one of the few molecules that can cross the blood-brain barrier. The researchers used it as the structural building block for the nanoparticles. They used synthetic molecules to link these proteins up and then attached the STAT3 inhibitor and a peptide called iRGD, which serves as a tumor homing device.

Over the course of three weeks, a cohort of mice received multiple doses of the new nanomedicine, extending their median survival to 41 days, up from 28 days for those untreated. Following that success, the researchers performed a second mouse study using the drug alongside today's current standard of care: focused radiotherapy. Seven of the eight mice reached long-term survival and appeared completely tumor-free, with no signs of malignant, invasive tumor cells.

"This is a huge step toward clinical implementation," said Maria Castro, a professor of neurosurgery and a co-senior author of the study. "This is the first study to demonstrate the ability to deliver therapeutic drugs systemically, or intravenously, that can also cross the blood-brain barrier to reach tumors."

The researchers said the synthetic protein nanoparticles could be adopted, after further development and preclinical testing, to deliver other small-molecule drugs and therapies to currently "undruggable" solid-based tumors.

Incidence of glioblastoma, the most common and aggressive form of brain cancer in adults, is rising in many countries. Today's median survival for patients with glioblastoma is around 18 months; the average 5-year survival rate is below 5 percent.

The study has been published in Nature Communications.