Lipid Nanoparticle-Mediated Targeted Delivery of MEGF10 siRNA to Astrocytes Reduced Synaptic Phagocytosis and Promoted Stroke Recovery in Mice

imaging and immunostaining results showed that injection of siMEGF10-LNP@AS1 efficiently delivered MEGF10 siRNA to astrocytes, downregulated MEGF10 expression in stroke mice, and reduced astrocytic phagocytosis of synapses. This intervention enhanced synaptic density while maintaining good biocompatibility. Furthermore, administration of siMEGF10-LNP@AS1 improved motor and cognitive function and reduced brain atrophy volume in stroke mice. Overall, our study establishes a robust platform for astrocyte-targeted gene modulation, offering a potential therapeutic strategy for CNS diseases.