Affiliation:
1. Department of Clinical Laboratory Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 P. R. China
2. Hubei Key Laboratory of Regenerative Medicine and Multi‐disciplinary Translational Research Research Center for Tissue Engineering and Regenerative Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 P. R. China
3. Department of Gastrointestinal Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 P. R. China
Abstract
AbstractFollowing stroke, oxidative stress induced by reactive oxygen species (ROS) aggravates neuronal damage and enlarges ischemic penumbra, which is devastating to stroke patients. Nanozyme‐based 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‐uptake abilities of neurons and barriers of organelle membranes, significantly limiting nanozymes’ neuroprotective effects. To overcome this limitation, a manganese‐organic framework modified with polydopamine (pDA‐MNOF), 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‐ROS effect, this nanozyme robustly decreases cellular ROS and effectively protects them from ROS‐induced injury. STAT‐3 signaling is found to play a vital role in pDA‐MNOF activating the two antioxidant enzymes, HO1 and SOD2. In vivo pDA‐MNOF 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‐MNOF activates vascular endothelial growth factor expression, a downstream target of STAT3 signaling, thus enhancing angiogenesis. Taken together, the biochemical, cell‐biological, and animal‐level behavioral data demonstrate the potentiality of pDA‐MNOF as a dual ROS‐scavenging agent for stroke treatment.
Funder
National Key Research and Development Program of China
Natural Science Foundation of Hubei Province
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
26 articles.
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