Mayo Clinic Experimental Dual-Drug Nanotherapy Crosses the Blood-Brain Barrier and Improved Survival in Preclinical Glioblastoma Models

Mayo Clinic researchers developed an experimental nanotherapy that delivers two cancer drugs directly to brain tumors, according to a study published in Nature Communications Medicine. The strategy extended survival in preclinical models of glioblastoma, the most aggressive form of brain cancer.

The nanotechnology-based approach packages two existing cancer drugs into tiny particles engineered to cross the brain's protective blood-brain barrier and target tumor cells. In preclinical models using patient-derived tissue, combining the treatment with radiation more than doubled survival compared with untreated controls.

Glioblastoma is notoriously difficult to treat. Patients typically survive for about 15 months after diagnosis, even with the latest therapies such as surgery, radiation and chemotherapy. One major challenge is that many drugs cannot effectively reach tumors in the brain, and those that do often lose effectiveness as tumors develop resistance.

The new approach uses small lipid-based particles, known as liposomes, to carry and deliver a combination of drugs — everolimus or rapamycin and vinorelbine — directly to cancer cells, using a new tumor-targeting strategy. By ensuring both drugs reach the same cells at the same time, researchers aim to improve tumor-killing effects while reducing the toxic side effects associated with higher drug doses.

"Glioblastoma remains extremely difficult to treat due to drug resistance and limited drug delivery to the brain," says Debabrata (Dev) Mukhopadhyay, Ph.D., a professor of biochemistry and molecular biology at Mayo Clinic in Florida. Dr. Mukhopadhyay, a nanotechnologist, is a senior author of the study. "Our approach is designed to improve both by targeting the tumor directly and combining therapies in a way that enhances their impact."

The drug combination includes agents that interfere with tumor growth pathways and disrupt the cancer's ability to repair DNA damage, making tumors more sensitive to radiation.

"This represents a promising direction for treating patients with glioblastoma and advancing new technologies and therapies, so we can one day improve the survival of patients with brain cancer by delivering novel cancer therapies to the brain," says Alfredo Quinones-Hiñojosa, M.D., dean of research emeritus and chair emeritus of the Department of Neurosurgery at Mayo Clinic in Florida and a senior author on the study. "Further research will be needed to determine whether these results translate to patients."

Researchers are conducting additional safety and dosing studies required before clinical trials can begin. If successful, the approach could eventually be an oral or intravenous medication used alongside standard treatments or as an option for patients whose tumors do not respond to existing therapies.

"While this work is still in development, it represents an important step toward developing more precise cancer treatments that are both more effective and less toxic, potentially improving quality of life for patients," says Dr. Mukhopadhyay.

This study was supported in part by the National Institutes of Neurologic Disorders and Stroke of the National Institutes of Health under award number R01NS129671. Read the study for a full list of authors, disclosures and funding.