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Here it is reported that Cu2Ir nanoparticles (NPs) with a Cu\u2010coordinated tetraphenylporphyrin (TPP) core and cyclometalated Ir(C^N)<jats:sub>2<\/jats:sub>(N^N) substituents integrate long\u2010lived near\u2010infrared (NIR) chemiluminescence (CL) imaging, photothermal therapy (PTT) and photodynamic therapy (PDT) for thrombolysis, with antioxidant and anti\u2010inflammatory properties. Based on density functional theory calculations the chemiluminescent reaction site between TPP and peroxynitrite (ONOO<jats:sup>\u2212<\/jats:sup>) is confirmed for the first time. The presence of the transition metal significantly improves the chemiluminescent properties of TPP. Upon specific activation by ONOO<jats:sup>\u2212<\/jats:sup>, Cu2Ir NPs exhibited more than 30\u2010fold NIR CL intensity than TPP NPs, and the luminescence lasted for 60\u00a0min allowing for precise and long\u2010lasting dynamic tracking of thrombi. Cu2Ir NPs achieved non\u2010invasive safe thrombolytic therapy triggered by NIR irradiation at the signaling site. 72.3% blood reperfusion is obtained for nearly complete restoration of blood flow, and re\u2010embolism is prevented in a mouse carotid artery model. Furthermore, Cu2Ir NPs scavenged excess reactive oxygen\/nitrogen species (RONS) and reduced inflammatory factors. Cu2Ir NPs hold promise as a single\u2010molecule strategy for diagnosing and treating diseases associated with thrombosis.<\/jats:p>","DOI":"10.1002\/advs.202501257","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T04:06:33Z","timestamp":1743221193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Endogenous Near\u2010Infrared Chemiluminescence: Imaging\u2010Guided Non\u2010Invasive Thrombolysis and Anti\u2010Inflammation Based on a Heteronuclear Transition Metal Complex"],"prefix":"10.1002","volume":"12","author":[{"given":"Ziwei","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province Department of Chemistry Northeast Normal University  5268 Renmin Street Changchun Jilin 130024 P. R. 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