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The activation of stimulator of interferon genes (STING) pathway has been thought a promising strategy to enhance immunotherapy efficacy. In this study, we adopted a comprehensive strategy that integrates innate immune responses with tumor\u2010targeting photothermal therapy (PTT) to simultaneously tackle multiple immune\u2010suppressive mechanisms in breast cancer. This semiconducting polymeric nanoagonists (DPTT\u2010Mn Lipo NPs) mediated PTT can effectively initiate tumor cell apoptosis and induce ICD, thereby reprogramming the immunosuppressive TME and activating STING. We confirmed the modulation of the TME through the PTT\u2010mediated ICD effect and the transactivation of the cGAS\u2010STING pathway in immune cells of the TME due to the released dsDNA via ICD, such as macrophages and DCs. Indeed, DPTT\u2010Mn Lipo NPs\u2010mediated PTT promoted M1 polarization of tumor\u2010associated macrophages, augmented T\u2010cell infiltration, facilitated dendritic cell (DC) maturation, and regulated type I interferon factor secretion, leading to efficient tumor suppression. Most importantly, the combination of DPTT\u2010Mn Lipo NPs\u2010based PTT with a checkpoint blockade therapy (anti\u2010PD\u20101) can elicit long\u2010term immune memory besides tumor eradication. Collectively, this nano\u2010system can systemically activate antitumor immunity through STING activation and potentially establish long\u2010term memory against tumor recurrence.<\/jats:p>","DOI":"10.1002\/adma.202406662","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T04:39:38Z","timestamp":1733287178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Engineering Semiconducting Polymeric Nanoagonists Potentiate cGAS\u2010STING Pathway Activation and Elicit Long Term Memory Against Recurrence in Breast Cancer"],"prefix":"10.1002","volume":"37","author":[{"given":"Haitao","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Hyperbaric Oxygen Medicine Guangdong Provincial Clinical Research Center for Geriatrics Shenzhen Clinical Research Center for Geriatric Shenzhen People's Hospital The First Affiliated Hospital Southern University of Science and Technology  Shenzhen Guangdong 518020 P. 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