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Their unique properties enable HEA nanoparticles to mimic the complex interactions of the redox homeostasis system, which is composed of cascade and multiple enzymatic reactions. The application of HEAs in mimicking complex enzymatic systems remains relatively unexplored, despite the importance of regulating biological redox reactions. Here, it is reported that ultra\u2010small (&lt;10 nm in a diameter) HEA nanozymes consisting of five platinum\u2010group metals with tunable morphologies from planar to dendritic structures are synthesized. The synthesized HEA nanozymes exhibited higher peroxidase\u2010like activity compared to monometallic platinum\u2010group nanoparticles. Additionally, HEA nanoparticles effectively mimicked RONS\u2010regulation metabolism in cascade reactions involving superoxide dismutase and catalase, as well as in multiple reactions including HORAC and NO scavenging. As a result, the HEA nanozyme exhibited superior anti\u2010inflammatory efficacy both in vitro and in vivo. The findings underscore the effectiveness of the high\u2010entropy alloy structure in restoring in vivo enzymatic systems through intrinsic activity enhancements and cascade reaction mechanisms.<\/jats:p>","DOI":"10.1002\/adhm.202402005","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T05:09:07Z","timestamp":1733461747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Ultrasmall High\u2010Entropy\u2010Alloy Nanozyme Catalyzed In Vivo ROS and NO Scavenging for Anti\u2010Inflammatory Therapy"],"prefix":"10.1002","volume":"14","author":[{"given":"Daeeun","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology (KAIST)  291 Daehak\u2013ro, Yuseong\u2013gu Daejeon 34141 Republic of 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