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Herein, we developed a near\u2010infrared light (NIR)\u2010triggered cascade effect system that enables precise spatiotemporal gene silencing and gas\u2010synergistic cancer therapy. This nanoplatform was constructed using an enzyme\u2010activatable DNAzyme, a nitric oxide (NO) precursor, and upconversion nanoparticles (UCNPs). The UCNPs act as light converters, facilitating the precursor to produce NO under NIR light irradiation, while the generated NO not only participates directly in gas therapy but also induces the upregulation of cytoplasmic APE1 level, resulting in enhanced DNAzyme activation and spatially controlled gene silencing. By leveraging this mechanism, cascade effects mediated gas\u2010gene synergistic therapy is achieved through the combination of NIR light\u2010controlled NO release and APE1\u2010activatable gene therapy. We demonstrated that this nanoplatform enables enhanced anti\u2010tumor effects both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This strategy represents a critical step forward in the quest for highly targeted and efficient cancer treatments.\n                  <\/jats:p>","DOI":"10.1002\/anie.202422375","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T03:24:44Z","timestamp":1733973884000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Near\u2010Infrared Light\u2010Triggered Cascade Nanosystems for Spatiotemporally Controlled Gene\u2010Silencing and Gas Synergistic Cancer Therapy"],"prefix":"10.1002","volume":"64","author":[{"given":"Yaru","family":"Cheng","sequence":"first","affiliation":[{"name":"Department Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging National-Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering Shenzhen University Medical School  Shenzhen 518060 China"},{"name":"Marshall Laboratory of Biomedical 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