Drug‐Free Biomimetic Oxygen Supply Nanovehicle Promotes Ischemia‐Reperfusion Therapy in Stroke

Abstract Recanalization intervention is the primary recommended therapy for ischemic stroke, but the rapid progression of brain damage results in a very narrow time window for ischemia‐reperfusion therapy, which remains the biggest obstacle for ischemic stroke treatment. Herein, a drug‐free biomimetic nanovehicle capable of improving cerebral ischemic tolerance and thus promoting ischemia‐reperfusion therapy is reported. The nanovehicle comprises an amphiphilic polyfluorocarbon, which delivers oxygen to alleviate the hostile hypoxic environment of ischemic brain, and Pluronic P123, which inhibits matrix metalloproteinase‐9 to protect the blood–brain barrier (BBB). When intravenously injected into ischemic stroke rats with transient middle cerebral artery occlusion, these nanovehicles are able to preferentially access cerebral ischemic lesions in an inflammation‐directed manner, conferring robust ischemic tolerance and reperfusion resistance of brain tissues for ischemia‐reperfusion therapy. Furthermore, it is also demonstrated that the nanovehicle is beneficial for mice with permanent ischemic stroke induced by photothrombosis. This work suggests a promising strategy with hypoxia relief and BBB protection for ischemic stroke therapy.