Loaded endogenous CO mimetic nanomedicine mitigates ischemic stroke ischemia-reperfusion injury

Ischemia-reperfusion injury is a major threat in ischemic stroke, with limited treatment options. Edaravone, a first-line drug, has multiple limitations, and the narrow time window for reperfusion therapy complicates treatment. This study reports a nanoparticle drug designed to mitigate ischemia-reperfusion injury by targeting inflammation. The drug is made of mesoporous silica (SiO2) loaded with the CO-releasing molecule CORM-401 and coated with a macrophage membrane (MM) shell. The nanoparticles effectively cross the blood-brain barrier and target ischemic brain lesions. In vitro and in vivo studies show that SiO2@MM@CORM-401 scavenges reactive oxygen species (ROS), promotes anti-inflammatory factor release, and inhibits pro-inflammatory factors. Additionally, CO helps prevent ferroptosis in the ischemic penumbra, offering a potential mechanism for alleviating ischemic stroke and providing a novel therapeutic approach. • Innovative nanoparticles cross blood-brain barrier to treat ischemic stroke effectively. • Macrophage membrane coating enhances targeting and neuroprotective capabilities. • Successfully suppresses ROS and inflammatory responses in experimental models. • Discovers carbon monoxide's ability to inhibit ferroptosis in brain tissue. • Shifts microglia from pro-inflammatory M1 to protective anti-inflammatory M2 state.