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Although nanoenzymes are explored as therapeutic candidates, conventional nanoenzymes predominantly target antioxidative mechanisms, which are insufficient to address the complex pathophysiology of ischemic stroke. In response to this challenge, this work introduces Transition Metal Nanocluster catalysts (TMNCs), which are widely recognized for their antioxidative and enzyme\u2010mimicking properties. However, this research reveals these nanoclusters, specifically molybdenum (Mo), vanadium (V) and tungsten (W), exhibit a novel and critical Deoxyribonuclease I (DNase1)\u2010like activity, previously unrecognized in the context of stroke therapy. Among these, Mo nanoclusters (Mo NCs) emerged as the most potent DNase1 mimics, efficiently degrading neutrophil extracellular traps (NETs) and disrupting the detrimental NET\u2010free radical cycle that exacerbates ischemic damage. This unique mechanism not only addresses oxidative stress but also mitigates NET\u2010associated inflammation, offering a dual\u2010action therapeutic approach. Behavioral studies in animal models demonstrated that Mo NCs significantly accelerated motor function recovery while providing robust neuroprotection.<\/jats:p>","DOI":"10.1002\/adhm.202500693","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T09:57:26Z","timestamp":1753955846000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["DNase1 Mimic TMNCs Disrupt Neutrophil Extracellular Traps and Free Radical Circulation for Ischemic Stroke Therapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Jiachen","family":"Sun","sequence":"first","affiliation":[{"name":"Third Affiliated Hospital of Jinzhou Medical University Jinzhou 121000 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baofeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Jinzhou Medical University Jinzhou 121000 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sen","family":"Lin","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Jinzhou Medical University Jinzhou 121000 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghao","family":"Ge","sequence":"additional","affiliation":[{"name":"Sports Medicine Center Department of Orthopedic Surgery\/Orthopedic Research Institute West China Hospital Sichuan University  Chengdu Sichuan 610064 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Cheng","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Jinzhou Medical University Jinzhou 121000 P. R. 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