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Nanozyme\u2010based antioxidants are emerging to treat stroke through scavenging excessive ROS. However, most of nanozymes cannot efficiently scavenge ROS in neuronal cytosol and mitochondria, due to low\u2010uptake abilities of neurons and barriers of organelle membranes, significantly limiting nanozymes\u2019 neuroprotective effects. To overcome this limitation, a manganese\u2010organic framework modified with polydopamine (pDA\u2010MNOF), capable of not only mimicking catalytic activities of natural SOD2's catalytic domain but also upregulating two endogenous antioxidant enzymes in neurons is fabricated. With such a dual anti\u2010ROS effect, this nanozyme robustly decreases cellular ROS and effectively protects them from ROS\u2010induced injury. STAT\u20103 signaling is found to play a vital role in pDA\u2010MNOF activating the two antioxidant enzymes, HO1 and SOD2. In vivo pDA\u2010MNOF treatment significantly improves the survival of middle cerebral artery occlusion (MCAo) mice by reducing infarct volume and more importantly, promotes animal behavioral recovery. Further, pDA\u2010MNOF activates vascular endothelial growth factor expression, a downstream target of STAT3 signaling, thus enhancing angiogenesis. Taken together, the biochemical, cell\u2010biological, and animal\u2010level behavioral data demonstrate the potentiality of pDA\u2010MNOF as a dual ROS\u2010scavenging agent for stroke treatment.<\/jats:p>","DOI":"10.1002\/advs.202206854","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T08:42:48Z","timestamp":1683016968000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["A Bioinspired Manganese\u2010Organic Framework Ameliorates Ischemic Stroke through its Intrinsic Nanozyme Activity and Upregulating Endogenous Antioxidant Enzymes"],"prefix":"10.1002","volume":"10","author":[{"given":"Jian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 P. R. 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