Synthetic protein nanoparticles can treat aggressive brain cancer

Reviewed by Emily Henderson, B.Sc.November 11, 2020

“I have been working in this field for over 10 years and have not seen anything like it.”

New research from the University of Michigan shows that a new synthetic protein nanoparticle that can slip past the nearly impermeable blood-brain barrier in mice could deliver anti-cancer drugs directly to malignant brain tumors.

The study is the first to demonstrate an intravenous drug capable of crossing the blood-brain barrier.

The discovery could one day allow for new clinical therapies for the treatment of glioblastoma, the most common and aggressive form of brain cancer in adults and whose incidence is increasing in many countries. Median survival today for patients with glioblastoma is approximately 18 months; the average 5-year survival rate is less than 5%.

Combined with radiation, the UM team’s intravenous injected therapy led to long-term survival in seven out of eight mice. When those seven mice experienced a recurrence of glioblastoma, their immune responses intervened to prevent the cancer from regrowing, without further therapeutic drugs or other clinical treatments.

“It’s still a miracle for us,” said Joerg Lahann, Wolfgang Pauli’s university professor of chemical engineering and senior co-author of the study. “Where we would expect to see some levels of tumor growth, they simply did not form when we resumed the challenge with mice. I have been working in this field for more than 10 years and have not seen anything like this.”

The findings suggest that the UM team’s combination of therapeutic drugs and nanoparticle delivery methods not only eradicated the primary tumor, but led to immunological memory or the ability to recognize and attack remaining malignant tumor cells more quickly.

This is a huge step towards clinical implementation. This is the first study to demonstrate the ability to administer therapeutic drugs systemically or intravenously, which can also cross the blood-brain barrier to reach tumors. “

Maria Castro, senior co-author of the study, collegiate professor of neurosurgery RC Schneider

Five years ago, Castro knew how he wanted to target glioblastoma. He wanted to stop a signal that cancer cells send, known as STAT3, to induce immune cells to grant them safe passage into the brain. If he could close that path with an inhibitor, the cancer cells would be exposed and the immune system could kill them. But he had no way of getting over the blood-brain barrier.

He attended a seminar at the Biointerfaces Institute, directed by Lahann, and the two discussed the problem. Lahann’s team began work on a nanoparticle capable of carrying a STAT3 inhibitor across the blood-brain barrier.

A protein called human serum albumin, which is present in the blood, is one of the few molecules capable of crossing the blood-brain barrier, so Lahann’s team used it as a building block for their nanoparticles. They used synthetic molecules to link these proteins and then linked the STAT3 inhibitor and a peptide called iRGD, which acts as a tumor-finding 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, compared with 28 days for untreated ones.

Following that success, the team performed a second study in mice using the drug alongside current standards of care: targeted radiation therapy. Seven of the eight mice achieved long-term survival and appeared completely tumor-free, with no signs of malignant and invasive cancer cells.

The researchers say their synthetic protein nanoparticles could be adopted, after further development and preclinical testing, to provide other drugs and small molecule therapies to currently “non-pharmacological” solid-based tumors.