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However, the highly adaptive nature and damage\u2010repair capabilities of malignant tumors strongly limit the efficacy of treatments based on a single treatment mode. To address this challenge, a self\u2010reinforced bimetallic Mito\u2010Jammer is developed by incorporating doxorubicin (DOX) and calcium peroxide (CaO\n                    <jats:sub>2<\/jats:sub>\n                    ) into hyaluronic acid (HA) \u2010modified metal\u2010organic frameworks (MOF). After cellular, Mito\u2010Jammer dissociates into CaO\n                    <jats:sub>2<\/jats:sub>\n                    and Cu\n                    <jats:sup>2+<\/jats:sup>\n                    in the tumor microenvironment. The exposed CaO\n                    <jats:sub>2<\/jats:sub>\n                    further yields hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    in a weakly acidic environment to strengthen the Cu\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010based Fenton\u2010like reaction. Furthermore, the combination of chemodynamic therapy and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    overload exacerbates ROS storms and mitochondrial damage, resulting in the downregulation of intracellular adenosine triphosphate (ATP) levels and blocking of Cu\u2010ATPase to sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic cell death and suppresses tumor metastasis simultaneously. This study presents a multivariate model for revolutionizing mitochondria damage, relying on the continuous retention of bimetallic ions to boost cuproptosis\/immunotherapy in cancer.\n                  <\/jats:p>","DOI":"10.1002\/advs.202306031","type":"journal-article","created":{"date-parts":[[2024,2,11]],"date-time":"2024-02-11T21:24:57Z","timestamp":1707686697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Self\u2010Reinforced Bimetallic Mito\u2010Jammer for Ca\n                    <sup>2+<\/sup>\n                    Overload\u2010Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization"],"prefix":"10.1002","volume":"11","author":[{"given":"Chier","family":"Du","sequence":"first","affiliation":[{"name":"Department of Ultrasound and Chongqing Key Laboratory of Ultrasound Molecular Imaging the Second Affiliated Hospital of Chongqing Medical University  Chongqing 400010 P. R. 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