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However, the lack of durable, DNA\u2010focused cytotoxic mechanisms hampers the translational efficacy of nanocatalytic therapy. Herein, we proposed a cascade nanocatalysis\u2010mediated strategy for endogenous amplification of apoptosis, achieved by an engineered metal organic framework nanomedicine (MOF\u2010Au\u2010L\u2010Arginine, abbreviated as MAL). The MOF serves both as a nanocatalyst and as a carrier for L\u2010Arginine (L\u2010Arg), while embedded Au nanoparticles enhance nanocatalyst reactivity. Subsequently, MOF catalyzes the generation of hydroxyl radicals (\u2022OH) and superoxide anions (O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2022\u2212<\/jats:sup>\n                    ), and then the O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2022\u2212<\/jats:sup>\n                    undergo a cascade reaction with NO released from L\u2010Arg, generating highly cytotoxic peroxynitrite (ONOO\u2013), which has greater cytotoxicity to tumor cells, can induce extensive DNA damage, and simultaneously impair DNA repair and disrupt the cell cycle. Genome\u2010wide RNA sequencing reveals MAL can activate the p53 pathway, thereby regulating apoptosis related proteins. In addition, MAL reduces mitochondrial membrane potential and promotes mitochondrial\u2010mediated apoptosis through the BAX\/Bcl\u20102\/caspase\u20103 axis, further amplifying endogenous apoptosis in tumor cells. In vivo, MAL effectively inhibits tumor growth with favorable biocompatibility.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520367","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T10:10:57Z","timestamp":1770804657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endogenous Amplification of Apoptosis via p53 Regulation using a Cascade Nanocatalytic Medicine"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1074-2757","authenticated-orcid":false,"given":"Tan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center For Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain\u2010Like Intelligence, School of Medicine, Shanghai Fourth People's Hospital Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center For Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain\u2010Like Intelligence, School of Medicine, Shanghai Fourth People's Hospital Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center For Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain\u2010Like Intelligence, School of Medicine, Shanghai Fourth People's Hospital Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center For Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain\u2010Like Intelligence, School of Medicine, Shanghai Fourth People's Hospital Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center For Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain\u2010Like Intelligence, School of Medicine, Shanghai Fourth People's Hospital Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8566-4847","authenticated-orcid":false,"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center For Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain\u2010Like Intelligence, School of Medicine, Shanghai Fourth People's Hospital Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, School of Medicine, Shanghai Fourth People's Hospital Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center For Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain\u2010Like Intelligence, School of Medicine, Shanghai Fourth People's Hospital Tongji University  Shanghai 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