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However, most chemiluminescence\u2010driven photodynamic therapy (CL\u2010PDT) systems typically rely on intracellular oxidants (e.g., H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) as chemiexcitation \u201cfuels\u201d, which conceptually contradicts the primary goal of elevating intratumoral oxidative stress. In this study, we report a sequential H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010triggered redox relay nano\u2010photosensitizer, NP\u2010Rubine, which addresses the fundamental \u201credox paradox\u201d by decoupling photon generation from oxidation consumption. Composed of an H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010responsive chemiluminescent probe (Rubine) and a\n                    <jats:italic>N<\/jats:italic>\n                    \u2010oxide scaffold (OPDEA\u2010Ppa), NP\u2010Rubine is selectively activated by endogenous H\n                    <jats:sub>2<\/jats:sub>\n                    S to initiate an efficiency chemiluminescence resonance energy transfer (CRET) cascade for efficient singlet oxygen (\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) production. Concurrently, the\n                    <jats:italic>N<\/jats:italic>\n                    \u2010oxide moiety promotes deep tumor penetration via transcytosis and depletes the intracellular NADPH pool. By synergistically coupling oxidant generation with reductant exhaustion, NP\u2010Rubine synergistically amplifies intracellular redox imbalance to induce apoptosis. In vivo studies substantiate that NP\u2010Rubine achieves exceptional deep\u2010tissue imaging and potent antitumor efficacy in HCT116 xenografts. This bio\u2010reductant, self\u2010sustained targeted CL\u2010PDT strategy circumvents the practical hurdles of oxidation\u2010fueled systems, offering a robust benchmark for precision nanomedicine in complex redox landscapes.\n                  <\/jats:p>","DOI":"10.1002\/anie.3027612","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:16:50Z","timestamp":1783437410000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequential H\n                    <sub>2<\/sub>\n                    S\u2010Triggered Redox Relay Nanoprobes for Self\u2010Sustained Chem\u2010Illuminating Cascade Photodynamic Therapy"],"prefix":"10.1002","volume":"65","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of 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