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However, the clinical translation of natural enzymes is hindered by inherent limitations, including poor stability and high immunogenicity. In this context, nanozymes have emerged as advanced tools for tumor therapy, with the development of cascade catalytic nanosystems representing a major research frontier. This study designed multifunctional copper\u2010caffeic acid metal\u2010phenolic networks (Cu\u2010CA MPNs). Upon lysosomal entry, the nanozyme mimics the neutrophil's SOD\u2010MPO cascade to continuously generate substantial reactive oxygen species (ROS), notably hypochlorous acid (HOCl). This process directly damages lysosomes, promotes mitochondrial ROS accumulation, and upregulates the expression of GSDMD\u2010N and GSDME\u2010N, ultimately triggering pyroptosis. Simultaneously, Cu\u2010CA MPNs released from ruptured lysosomes cause abnormal copper ion accumulation within mitochondria. This enhances oligomerization of the DLAT protein and downregulates key metabolic proteins\u2010including ACO2, ETFDH, LIAS, and FDX1\u2010thereby inducing cuproptosis. In a tumor\u2010bearing mouse model, Cu\u2010CA MPNs demonstrated potent antitumor efficacy and favorable biosafety. This work provides a new perspective for tumor catalytic therapy using nanozymes that simulate the neutrophil enzymatic cascade.<\/jats:p>","DOI":"10.1002\/adhm.202505342","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:23:56Z","timestamp":1783052636000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Biomimetic Copper\u2010Caffeic Acid Nanozyme Activates Cuproptosis and Pyroptosis by Mimicking the Neutrophil Enzymatic Cascade"],"prefix":"10.1002","volume":"15","author":[{"given":"Yangyang","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Oncology The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Yichun University  Yichun 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