Reviewed by Lexie CornerApr 24 2025
In a latest examine printed in Small, researchers on the College of Michigan developed nanodiscs designed to focus on levels of cholesterol inside GBM tumors. This strategy successfully starves the most cancers cells and has proven promise in rising the survival charges of handled mice.
Jacob Dwyer. Picture Credit score: Michigan Drugs
Glioblastoma multiforme (GBM) is a extremely aggressive mind tumor primarily affecting adults. Round 30,000 people within the US obtain a GBM analysis yearly, and the 5-year survival price for sufferers is just 7 %.
Present therapy approaches contain surgical procedure, radiation remedy, and chemotherapy utilizing temozolomide. Nonetheless, none of those strategies presently supply a remedy for GBM.
Therapy choices for GBM have their limitations.
Maria Castro, Professor, Neurosurgery and Member, Rogel Most cancers Heart
“Though surgical procedure will help enhance survival, surgeons usually should take away the traditional tissue that surrounds the tumor to forestall it from spreading. Alternatively, utilizing medicine to focus on the most cancers can be difficult as a result of GBM cells are heterogeneous. In case you try to goal a selected pathway, the most cancers cells can use different pathways and repopulate the tumor,” mentioned Castro.
Based on Pharmaceutical Sciences Professor Anna Schwendeman, one other vital problem is that many anti-cancer medicine battle to penetrate the blood-brain barrier. This protecting mechanism prevents numerous substances within the bloodstream from getting into the mind.
Nanodiscs Cut back Ldl cholesterol Ranges in GBM Cells
Earlier analysis has indicated that GBM tumors rely on ldl cholesterol for his or her progress and multiplication. Nonetheless, these tumors can’t produce enough ldl cholesterol themselves and as an alternative depend on importing it from surrounding cells.
Constructing on this understanding, the analysis crew engineered particular nanodiscs and administered them to mouse fashions with GBM.
Our aim was to supply surgeons with the choice to inject these particles into the tumor cavity after they’ve eliminated the tumor mass.
Troy Halseth, Former Graduate Scholar and Examine Co-First Writer, Rogel Most cancers Heart
“You will need to concentrate on native supply as a result of chemotherapy medicine are poisonous and may trigger a number of negative effects,” mentioned Halseth.
The researchers designed nanodiscs to ship Liver-X-Receptor (LXR) agonists on to most cancers cells. These molecules work by rising the variety of mobile pumps accountable for eradicating ldl cholesterol from the tumor cells, resulting in their destruction.
When mixed with radiation remedy, the nanodisc therapy resulted in over 60 % survival in mice, an enchancment in comparison with the mice that solely acquired radiation.
“We included radiation as a result of it’s the usual process of look after GBM sufferers. Subsequently, any new remedy have to be given along with radiation,” mentioned Anzar Mujeeb, a postdoctoral fellow within the Castro lab and co-first writer on the examine.
The mixed therapy preserved regular mind construction and didn’t lead to any observable opposed negative effects within the mice.
Nanodiscs Increase the Immune Response In opposition to GBM Tumors
The nanoparticles have been engineered to show CpG oligonucleotides on their floor, molecules that stimulate the physique’s immune system.
Because of this, immune cells goal and assault the present tumor and develop an immunological reminiscence, permitting them to acknowledge and assault any future tumor progress.
“The primary reason behind dying in glioma sufferers shouldn’t be the first most cancers, which is normally eliminated effectively by surgeons. As an alternative, it’s when the tumor comes again. We needed to deal with that drawback as effectively,” mentioned Castro.
The researchers discovered that, along with extending survival, the nanodiscs triggered immune reminiscence. Remarkably, 68 % of the surviving mice have been capable of get rid of a second tumor that was later launched into their techniques.
The analysis crew is now centered on rising nanoparticle manufacturing and planning a medical trial.
“This examine wouldn’t have been attainable with out the interdisciplinary collaboration between U-M most cancers biologists and drug supply consultants from the College of Pharmacy,” mentioned Schwendeman.
Extra authors embrace Lisha Liu, Kaushik Banerjee, Nigel Lang, Todd Hollon, Minzhi Yu, Mark Vander Roest, Ling Mei, Hongliang He, and Maya Sheth.
The examine was supported by Nationwide Institutes of Well being and Nationwide Institute of Neurological Problems and Stroke grants and the Rogel Most cancers Heart Scholar Award. The examine was additionally supported by the Biosciences Initiative in Mind Most cancers Applied sciences, U-M Division of Neurosurgery, Pediatric Mind Tumor Basis, and Ian’s Mates Basis.
Journal Reference:
Liu, L., et al. (2025) HDL Nanodiscs Loaded with Liver X Receptor Agonist Decreases Tumor Burden 1 and Mediates Lengthy-term Survival in Mouse Glioma Mannequin. Small. doi.org/10.1002/small.202307097
