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Oxidative stress induced by the excessive generation of reactive oxygen species (ROS) leads to periodontitis, which is closely associated with pathological processes, including mitochondrial dysfunction of periodontal cells and local immune dysregulation. However, current treatment modalities that target single pathological processes have limited long\u2010term therapeutic effects. Herein, a multifunctional Yolk\u2013Shell nanozyme, Au@CeO<jats:sub>2<\/jats:sub>\u2010dimethyl fumarate (DMF), which comprehensively addresses the oxidative stress\u2010induced pathophysiological processes of periodontitis through antioxidant activity, mitochondrial maintenance, and immune modulation mechanisms, is described. For material design logic, functionally complementary Au and CeO<jats:sub>2<\/jats:sub>\u00a0formed an excellent photothermally regulated high\u2010efficiency nanozyme, which also provided an ideal drug carrier for DMF. As for the therapeutic logic, Au@CeO<jats:sub>2<\/jats:sub>\u2010DMF restores mitochondrial dysfunction and immune dysregulation, which also contributes to endogenous ROS elimination, thereby achieving long\u2010term stable therapeutic effects. In a rat model, local Au@CeO<jats:sub>2<\/jats:sub>\u2010DMF photothermal therapy effectively alleviated ROS\u2010induced tissue damage and restored periodontal homeostasis. Altogether, this study presents a novel antioxidant nanozyme for managing alveolar bone loss under prolonged oxidative stress and demonstrates the importance of comprehensive intervention in key pathological processes in periodontitis treatment design.<\/jats:p>","DOI":"10.1002\/advs.202413891","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T03:30:22Z","timestamp":1735011022000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Triple\u2010Combination Therapy with a Multifunctional Yolk\u2013Shell Nanozyme Au@CeO<sub>2<\/sub> Loaded with Dimethyl Fumarate for Periodontitis"],"prefix":"10.1002","volume":"12","author":[{"given":"Tiancheng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthodontics Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology National Center for Stomatology National Clinical 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