Stem Cell Membrane–Coated Nanodrugs with Nicotinamide Riboside Targets Alzheimer's Disease: Preclinical Findings

Synopsis

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that urgently requires more effective, precisely targeted treatments. This study developed a biomimetic nanomedicine designed to target microglia, the brain’s immune cells responsible for clearing toxic proteins like amyloid-β (Aβ). The new delivery system—called Gas6-NV-NPs—uses nanoparticles made from poly(lactic-co-glycolic acid) (PLGA) loaded with two therapeutic agents: rapamycin (RAP), which reduces inflammation, and nicotinamide riboside (NR), a vitamin B3–derived NAD+ booster that supports mitochondrial health and neuron repair. These nanoparticles are coated with membranes from Gas6-overexpressing neural stem cells, which help them bind specifically to microglia and avoid immune clearance. In both cell and animal models of AD, Gas6-NV-NPs restored lysosomal function, enhanced microglial clearance of Aβ, and reduced neuroinflammation, leading to improved neuronal survival and repair in AD mice. This innovative dual-drug, biomimetic nanotherapy effectively delivers NR and RAP to the brain, offering a powerful multitarget approach to combat Alzheimer’s pathology.

Journal

ACS Applied Materials & Interfaces