Membrane-camouflaged metal-phenolic nanomedicines for the treatment of ischemic stroke via relieving oxidative stress and neuroinflammation.

Ischemia-reperfusion injury (IRI) following thrombolytic therapy significantly influences the ischemic stroke outcomes. Here, we develop M@EFE NPs, a biomimetic nanomedicine, to alleviate the reperfusion injury. This nanomedicine is constructed by encapsulating Edaravone into the metal-phenolic nanoparticles self-assembled from epigallocatechin gallate (EGCG) and iron ions (Fe3+), and further coating with macrophage membranes. This design integrates the antioxidant and anti-lipid peroxidation properties of the EGCG-Fe3+ nanoparticles with the inflammatory targeting capacity of macrophage membranes. Following systemic administration, M@EFE NPs are able to penetrate the blood-brain barrier and target the ischemic regions, thereby inhibiting oxidative damage, protecting neurons, and ultimately improving stroke outcomes. In vitro, the nanomedicine can effectively scavenge reactive oxygen species, inhibit lipid peroxidation, and enhance cell survival. In murine middle cerebral artery occlusion models, M@EFE NPs could reduce infarct volume, attenuate neuronal apoptosis and neuroinflammation, and improve motor recovery and long-term survival. This study presents a promising combinatorial nanotherapeutic strategy for ischemic stroke, providing insights into biomimetic nanomedicine for treating cerebral IRI.