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Here we report a triple\u2011stage precision nanogel (CDX@nano) in which carbon dots (CDs) serve as organelle\u2011targeted delivery vehicles. The nanogel is surface\u2010functionalized with indomethacin for tumor\u2011specific homing and encapsulates CDs conjugated with doxorubicin (DOX) via glutathione\u2010cleavable disulfide linkages. Upon near\u2010infrared irradiation, the CDs generate singlet oxygen, triggering nanogel disassembly, and rapid drug release. The liberated CDs accumulate in mitochondria, elevating reactive oxygen species and disrupting redox homeostasis, while DOX translocates to the nucleus to induce DNA damage. This cascade\u2010activated, dual\u2010compartment assault integrates photodynamic and chemotherapeutic modalities. In vitro, CDX@nano reduced tumor cell viability to 8.5% upon irradiation, showing approximately 4.5\u2011fold greater potency than non\u2010targeted controls. In vivo, it achieved over 85% tumor growth inhibition with minimal systemic toxicity. This triple\u2010stage platform offers a promising strategy to overcome key barriers in cancer therapy.<\/jats:p>","DOI":"10.1002\/adhm.71465","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:03:35Z","timestamp":1784628215000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Triple\u2010Stage Precision Carbon Dot Nanogel With Cascade Activation for Spatiotemporally Controlled Chemo\u2013Photodynamic Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Yunxiao","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Fine Chemicals Dalian University of Technology  Dalian China"},{"name":"Ningbo Institute of Dalian University of Technology  Ningbo 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