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Here, we report a structurally well\u2010defined and highly functional single\u2010site copper(I) nanomodulators termed CuNTD, constructed by precisely anchoring atomically dispersed self\u2010assembly S\u2010Cu(I)\u2010S sites onto a two\u2010dimensional Ti\n                    <jats:sub>3<\/jats:sub>\n                    C\n                    <jats:sub>2<\/jats:sub>\n                    surface. Leveraging Cu\n                    <jats:sup>+<\/jats:sup>\n                    with a higher catalytic efficiency than Cu\n                    <jats:sup>2+<\/jats:sup>\n                    , CuNTD generates reactive oxygen species (ROS) storms through photothermal\u2010enhanced cascade catalysis, further inducing mitochondrial dysfunction, ferroptosis and cuproptosis. Multifunctional CuNTD triggers strong ICD through cascade\u2010regulatory pathways of photothermal\u2010amplified ROS storms, cuproptosis and ferroptosis, effectively promoting dendritic cell maturation while reducing monotherapies side effects and resistance. In vivo, CuNTD combined with FDA\u2010approved immunoadjuvants significantly prolong the survival of mice. With its demonstrated biosafety and high efficiency as an ICD inducer, this study provides a promising framework for advancing augmented tumor immunotherapy with significant clinical potential.\n                  <\/jats:p>","DOI":"10.1002\/exp.20240275","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T17:43:40Z","timestamp":1741715020000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Spatial Isolation of Single Copper(I) Sites for Cascade Enzyme\u2010Like Catalysis and Simultaneous Ferroptosis\/Cuproptosis Boosted Immunotherapy"],"prefix":"10.1002","volume":"5","author":[{"given":"Yuanyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research Shenzhen Institute of Translational Medicine The First Affiliated Hospital of Shenzhen University Shenzhen Second People's 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