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Overproduction of reactive oxygen species (ROS) during reperfusion in ischemic stroke (IS) severely impedes neuronal survival and results in excessive rates of morbidity and disability. The efficient blood-mind barrier (BBB) penetration and brain supply of antioxidative agents remain the largest challenge in treating ischemic reperfusion-induced cerebrovascular and neural damage. On this study, a metallic-natural framework (MOF) nanozyme (MIL-101-NH2(Fe/Cu)) with ROS scavenging activities to encapsulate neuroprotective agent rapamycin is fabricated and decorating the exterior with BBB-concentrating on protein ligands (transferrin), thereby realizing enhanced drug retention and controlled release inside ischemic lesions for the synergistic treatment of IS. Through the receptor-mediated transcellular pathway, the transferrin-coated MOF nanoparticles achieved efficient transport across the BBB and focused accumulation on the cerebral ischemic damage site of mice with middle cerebral artery occlusion/reperfusion (MCAO/R), wherein the nanocarrier exhibited catalytic actions of ROS decomposition into O2 and H2O2-responsive rapamycin launch. By its BBB-focusing on, antioxidative, anti-inflammatory, and antiapoptotic properties, the MOF nanosystem addressed multiple pathological factors of IS and realized outstanding neuroprotective results, resulting in the substantial reduction of cerebral infarction volume and accelerated recovery of nerve capabilities within the MCAO/R mouse model. This MOF-primarily based nanomedicine supplies priceless design ideas for efficient IS therapy with multi-mechanism synergies.
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發表於 2025-9-8 06:08:18