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In this paper, a mitochondrial complex biomimetic nanozyme (MCBN), which plays the role of an artificial \u201cVI\u201d complex and acts as an electron and free radical conversion factory to regulate ETC homeostasis is creatively developed. MCBN is composed of bovine serum albumin (BSA), polyethylene glycol (PEG), and triphenylphosphine (TPP) hierarchically encapsulating MnO<jats:sub>2<\/jats:sub> polycrystalline particles. It has nanoscale size and biological properties like natural complexes. In vivo and in vitro experiments confirm that MCBN can target the mitochondrial complexes of inflammatory macrophages, absorb excess electrons in ETC, and convert the electrons to decompose H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. By reducing the ROS and ATP bursts and converting existing free radicals, inhibiting NLRP3 inflammatory vesicle activation and NF\u2010<jats:italic>\u03ba<\/jats:italic>B signaling pathway, MCBN effectively suppresses macrophage M1 activation and inflammatory factor secretion. It also demonstrates good inflammation control and significantly alleviates alveolar bone loss in a mouse model of ligation\u2010induced periodontitis. This is the first nanozyme that mimics the mitochondrial complex and regulates ETC, demonstrating the potential application of MCBN in immune diseases.<\/jats:p>","DOI":"10.1002\/adhm.202304125","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T16:04:35Z","timestamp":1706803475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Mn\u2010Based Artificial Mitochondrial Complex \u201cVI\u201d Acts as an Electron and Free Radical Conversion Factory to Suppress Macrophage Inflammatory Response"],"prefix":"10.1002","volume":"13","author":[{"given":"Mingxing","family":"Ren","sequence":"first","affiliation":[{"name":"College of Stomatology Chongqing Medical University Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education  Chongqing 401147 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