Neurology and Neurosurgery

May 27, 2026

Mayo Clinic researchers have developed a nanotherapy that delivers two cancer drugs directly to glioblastoma multiforme (GBM) tumors and makes them better respond to radiation therapy. As described in Communications Medicine, the experimental therapy extended survival in laboratory preclinical models and might provide a promising new approach for treating GBM in patients.

GBM is notoriously resistant to treatment due to tumor heterogeneity and the blood-brain barrier's ability to prevent many chemotherapeutic agents from reaching tumor sites. Combination therapy offers significant potential by targeting multiple signaling pathways. Mayo Clinic's experimental approach packages two existing cancer drugs into nanoparticles engineered to cross the blood-brain barrier and target tumor cells.

The Mayo Clinic researchers developed a tumor-targeted liposomal (TTL) nanoformulation, using a proprietary tumor-targeting peptide. The TTL was loaded with everolimus (TTL-E), vinorelbine (TTL-V), rapamycin (TTL-R) or a combination (TTL-EV or TTL-RV). The formulations were tested in vivo on orthotopic GBM mice, combined with temozolomide and radiation. RNA sequencing was performed to identify molecular and transcriptome changes posttreatment.

Key findings:

• The TTL nanoformulation demonstrated tumor-specific uptake, effectively delivering drugs to GBM tumors.
• TTL-EV and TTL-RV outperformed single-drug formulations.
• Radiation combined with TTL-EV or TTL-RV enhanced tumor suppression and survival in GBM models, while temozolomide provided little benefit.
• Gene expression analysis identified differentially expressed genes linked to DNA damage and cell death.
• Mechanistic studies suggested that TTL-EV plus radiation inhibits cell growth and proliferation pathways, while also sensitizing GBM to radiation.
• Transcriptome analysis revealed differentially expressed genes linked to DNA damage repair, cell cycle, metabolism and extracellular matrix pathways.

"Our approach is designed to target the tumor directly and combine therapies in a way that enhances their impact, " says Dev Mukhopadhyay, Ph.D., a nanotechnologist-biochemist at Mayo Clinic in Jacksonville, Florida, and the study's senior author.

"These results represent a promising direction for treating patients with this devastating brain cancer," says Alfredo Quinones-Hinojosa, M.D., a neurosurgeon at Mayo Clinic in Jacksonville, Florida, and a study collaborator. "By advancing new technologies and therapies, we might one day deliver novel cancer therapies to the brain and improve patient survival."

For more information

Angom RS, et al. Surface-engineered dual drug-loaded tumor-targeted liposomal nanoparticles to overcome the therapeutic resistance in glioblastoma multiforme. Communications Medicine. 2026;6:152.

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