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However, its clinical effectiveness remains limited by poor drug delivery efficiency, severe adverse effects, and emerging chemoresistance. To overcome these limitations, a triple\u2010drug co\u2010delivery system (NP3) is designed, encapsulating Cis prodrug (Cis(IV)), curcumin (Cur), and manganese ions within reactive oxygen species (ROS)\u2010responsive nanoparticles (NPs). NP3 efficiently accumulated at tumor sites and rapidly released its therapeutic payload upon endocytosis, triggered by abundant intracellular ROS. After NP3 degradation, Cis in combination with Cur induced significant DNA damage. This DNA debris subsequently activated the cGAS\u2010STING pathway, enhancing tumor immunogenicity. Additionally, manganese ions functioned as immune adjuvants, further amplifying cGAS\u2010STING activation. Consequently, NP3 promoted dendritic cell (DC) maturation, enhanced the infiltration of CD8+ T\u2010cells, and concurrently decreased the infiltration of immunosuppressive cells. In an OS mouse model, combining NP3 with anti\u2010PD\u2010L1 treatment markedly improved both tumor suppression and immune system activation. RNA sequencing analysis demonstrated that NP3 synergistically promoted tumor regression by concurrently inducing pro\u2010apoptotic signaling and immune responses. In conclusion, this study presents an innovative therapeutic strategy combining targeted chemotherapy delivery with robust antitumor metalloimmunotherapy, offering a promising therapeutic approach for OS.<\/jats:p>","DOI":"10.1002\/adhm.202504555","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T11:25:39Z","timestamp":1764761139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Co\u2010Delivery of Cisplatin and Curcumin via ROS\u2010Responsive Nanoparticles to Activate the cGAS\u2010STING Pathway for Osteosarcoma Metalloimmunotherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Yanan","family":"Wu","sequence":"first","affiliation":[{"name":"Senior Department of Orthopedics Chinese PLA General Hospital  Beijing P. R. China"},{"name":"Medical School of Chinese PLA  Beijing P. R. 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