Biomimetic M2 Microglia Membrane-Coated Nanoplatform for Immune Reprogramming and Targeted Edaravone Delivery in Ischemic Stroke

Ischemic stroke is a major cause of death and long-term disability worldwide, in which oxidative stress and neuroinflammation contribute substantially to secondary neuronal injury. Edaravone (EDA), a clinically approved free radical scavenger, has shown neuroprotective potential in ischemic stroke; however, its therapeutic efficacy is hindered by a short half-life, limited blood-brain barrier (BBB) penetration, and off-target effects. To overcome these limitations, we developed a biomimetic nanoplatform by encapsulating EDA within a nanoparticle core and coating it with membranes derived from M2-polarized microglia (EDA@M2 NPs). This hybrid system integrates potent antioxidant activity with inflammation-targeting and immunomodulatory capabilities. In a mouse model of middle cerebral artery occlusion (MCAO), EDA@M2 NPs selectively accumulated in the ischemic hemisphere, significantly reduced infarct volume, suppressed neuronal apoptosis, and improved neurological outcomes. Mechanistically, the nanoplatform not only scavenged excessive reactive oxygen species (ROS) but also reprogrammed microglia from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby mitigating secondary neuroinflammation. By integrating targeted delivery, oxidative stress attenuation, and immune microenvironment remodeling, this combinatorial therapeutic strategy markedly enhanced neuroprotection after ischemic stroke. Our findings demonstrate the translational promise of biomimetic nanotherapeutics for effective ischemic brain injury intervention.