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Overproduction of reactive oxygen species (ROS) throughout reperfusion in ischemic stroke (IS) severely impedes neuronal survival and leads to high rates of morbidity and disability. The efficient blood-brain barrier (BBB) penetration and brain delivery of antioxidative brokers remain the most important problem in treating ischemic reperfusion-induced cerebrovascular and neural injury. On this research, a metallic-natural framework (MOF) nanozyme (MIL-101-NH2(Fe/Cu)) with ROS scavenging actions to encapsulate neuroprotective agent rapamycin is fabricated and decorating the exterior with BBB-concentrating on protein ligands (transferrin), thereby realizing enhanced drug retention and managed launch inside ischemic lesions for the synergistic therapy of IS. Through the receptor-mediated transcellular pathway, the transferrin-coated MOF nanoparticles achieved environment friendly transport across the BBB and targeted accumulation on the cerebral ischemic damage site of mice with center cerebral artery occlusion/reperfusion (MCAO/R), whereby the nanocarrier exhibited catalytic actions of ROS decomposition into O2 and H2O2-responsive rapamycin release. By its BBB-concentrating on, antioxidative, anti-inflammatory, and antiapoptotic properties, the MOF nanosystem addressed multiple pathological factors of IS and realized outstanding neuroprotective results, leading to the substantial discount of cerebral infarction quantity and accelerated restoration of nerve features within the MCAO/R mouse model. This MOF-based mostly nanomedicine offers invaluable design principles for efficient IS therapy with multi-mechanism synergies.
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