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Herein, we report a near\u2010infrared (NIR)\u2010gated nanogenerator (Cy\u2010NO NPs) engineered for low\u2010dose, NO\u2010potentiated multi\u2010modal cancer phototherapy. By anchoring a thiol\u2010functionalized ortho\u2010trifluoromethyl\u2010nitroaromatic moiety onto a cyanine (IR825) scaffold, the design ensures negligible NO leakage under oxidative, reductive, and thermal stresses, thereby eliminating systemic toxicity. Upon 808\u00a0nm excitation, the excited\u2010state energy dissipation is balanced to drive four concurrent pathways: (i) a photoinduced intramolecular electron transfer (PIET) process triggering a nitro\u2010to\u2010nitrite rearrangement for NO release; (ii) Type I &amp; II photodynamic effects; (iii) photothermal conversion; and (iv) NIR\u2010II fluorescence emission. The released NO reacts in situ with simultaneous superoxide (O\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2022\u2212<\/jats:sup>\n                    ) bursts to yield highly cytotoxic peroxynitrites (ONOO\n                    <jats:sup>\u2212<\/jats:sup>\n                    ). This synergistic ROS\/RNS surge targets mitochondria, inducing membrane depolarization and rapid ATP depletion to trigger apoptosis. Guided by NIR\u2010II fluorescence imaging, this multi\u2010modal therapy achieves efficient tumor ablation in vivo, validating a potent low\u2010dose strategy for integrating controlled gas release with phototherapy.\n                  <\/jats:p>","DOI":"10.1002\/anie.7993582","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:03:34Z","timestamp":1776085414000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A NIR\u2010Gated Nanogenerator Enables Low\u2010Dose Nitric Oxide\u2010Potentiated Phototherapy"],"prefix":"10.1002","volume":"65","author":[{"given":"Yanxin","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemical Resource Engineering Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical Technology  Beijing 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