Reviewed by Lexie CornerApr 24 2025
In a recent study published in Small, researchers at the University of Michigan developed nanodiscs designed to target cholesterol levels within GBM tumors. This approach effectively starves the cancer cells and has shown promise in increasing the survival rates of treated mice.
Jacob Dwyer. Image Credit: Michigan Medicine
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor primarily affecting adults. Around 30,000 individuals in the US receive a GBM diagnosis annually, and the 5-year survival rate for patients is only 7 %.
Current treatment approaches involve surgery, radiation therapy, and chemotherapy using temozolomide. However, none of these methods currently offer a cure for GBM.
Treatment options for GBM have their limitations.
Maria Castro, Professor, Neurosurgery and Member, Rogel Cancer Center
“Although surgery can help improve survival, surgeons often have to remove the normal tissue that surrounds the tumor to prevent it from spreading. On the other hand, using drugs to target the cancer is also challenging because GBM cells are heterogeneous. If you try and target a particular pathway, the cancer cells can use other pathways and repopulate the tumor,” said Castro.
According to Pharmaceutical Sciences Professor Anna Schwendeman, another significant challenge is that many anti-cancer drugs struggle to penetrate the blood-brain barrier. This protective mechanism prevents various substances in the bloodstream from entering the brain.
Nanodiscs Reduce Cholesterol Levels in GBM Cells
Earlier research has indicated that GBM tumors depend on cholesterol for their growth and multiplication. However, these tumors cannot produce sufficient cholesterol themselves and instead rely on importing it from surrounding cells.
Building on this understanding, the research team engineered specific nanodiscs and administered them to mouse models with GBM.
Our goal was to provide surgeons with the option to inject these particles into the tumor cavity after they have removed the tumor mass.
Troy Halseth, Former Graduate Student and Study Co-First Author, Rogel Cancer Center
“It is important to focus on local delivery because chemotherapy drugs are toxic and can cause several side effects,” said Halseth.
The researchers designed nanodiscs to deliver Liver-X-Receptor (LXR) agonists directly to cancer cells. These molecules work by increasing the number of cellular pumps responsible for removing cholesterol from the tumor cells, leading to their destruction.
When combined with radiation therapy, the nanodisc treatment resulted in over 60 % survival in mice, an improvement compared to the mice that only received radiation.
“We included radiation because it is the standard procedure of care for GBM patients. Therefore, any new therapy must be given in addition to radiation,” said Anzar Mujeeb, a postdoctoral fellow in the Castro lab and co-first author on the study.
The combined treatment preserved normal brain structure and did not result in any observable adverse side effects in the mice.
Nanodiscs Boost the Immune Response Against GBM Tumors
The nanoparticles were engineered to display CpG oligonucleotides on their surface, molecules that stimulate the body’s immune system.
As a result, immune cells target and attack the existing tumor and develop an immunological memory, allowing them to recognize and attack any future tumor growth.
“The main cause of death in glioma patients is not the primary cancer, which is usually removed efficiently by surgeons. Instead, it is when the tumor comes back. We wanted to address that problem as well,” said Castro.
The researchers found that, in addition to extending survival, the nanodiscs triggered immune memory. Remarkably, 68 % of the surviving mice were able to eliminate a second tumor that was later introduced into their systems.
The research team is now focused on increasing nanoparticle production and planning a clinical trial.
“This study would not have been possible without the interdisciplinary collaboration between U-M cancer biologists and drug delivery experts from the School of Pharmacy,” said Schwendeman.
Additional authors include Lisha Liu, Kaushik Banerjee, Nigel Lang, Todd Hollon, Minzhi Yu, Mark Vander Roest, Ling Mei, Hongliang He, and Maya Sheth.
The study was supported by National Institutes of Health and National Institute of Neurological Disorders and Stroke grants and the Rogel Cancer Center Scholar Award. The study was also supported by the Biosciences Initiative in Brain Cancer Technologies, U-M Department of Neurosurgery, Pediatric Brain Tumor Foundation, and Ian's Friends Foundation.
Journal Reference:
Liu, L., et al. (2025) HDL Nanodiscs Loaded with Liver X Receptor Agonist Decreases Tumor Burden 1 and Mediates Long-term Survival in Mouse Glioma Model. Small. doi.org/10.1002/small.202307097