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May 28, 2022 07:00 am

Scientists Use Nanoparticles To Break Through Shield That Brain Tumors Use To Avoid Detection By the Immune System

Scientists from the University of Michigan have "fabricated a nanoparticle to deliver an inhibitor to brain tumor in mouse models, where the drug successfully turned on the immune system to eliminate the cancer," reports ScienceDaily. "The process also triggered immune memory so that a reintroduced tumor was eliminated -- a sign that this potential new approach could not only treat brain tumors but prevent or delay recurrences." From the report: The small molecule inhibitor AMD3100 was developed to block the action of CXCR12, a cytokine released by the glioma cells that builds up a shield around the immune system, preventing it from firing up against the invading tumor. Researchers showed in mouse models of glioma that AMD3100 prevented CXCR12 from binding with immune-suppressive myeloid cells. By disarming these cells, the immune system remains intact and can attack the tumor cells. But AMD3100 was having trouble getting to the tumor. The drug did not travel well through the bloodstream, and it did not pass the blood brain barrier, a key issue with getting drugs into the brain. The Castro-Lowenstein lab collaborated with Joerg Lahann, Ph.D., Wolfgang Pauli Collegiate Professor of Chemical Engineering at the U-M College of Engineering, to create protein-based nanoparticles to encapsulate the inhibitor, in the hopes of helping it pass through the bloodstream. Castro also connected with Anuska V. Andjelkovic, M.D., Ph.D., professor of pathology and research professor of neurosurgery at Michigan Medicine, whose research focuses on the blood brain barrier. They noted that glioma tumors create abnormal blood vessels, interfering with normal blood flow. The researchers injected AMD3100-loaded nanoparticles into mice with gliomas. The nanoparticles contained a peptide on the surface that binds to a protein found mostly on the brain tumor cells. As the nanoparticles traveled through the bloodstream toward the tumor, they released AMD3100, which restored the integrity of the blood vessels. The nanoparticles could then reach their target, where they released the drug, thus blocking the entry of the immune-suppressive myeloid cells into the tumor mass. This allowed the immune cells to kill the tumor and delay its progression. [...] Among the mice whose tumors were eliminated, the researchers then reintroduced the tumor, simulating a recurrence. Without any additional therapy, 60% of mice remained cancer-free. The research has been published in the journal ACS Nano.

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