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To enhance immune infiltration, mild photothermal therapy (PTT) is often combined with immunotherapy. However, the impact of mild PTT on the TME remains unclear. The bioinformatics analyses reveal that mild PTT amplifies immune cell infiltration and stimulates T\u2010cell activity. Notably, it accelerates the release of tumor cell\u2010derived exosomes (T\n                    <jats:sub>EX<\/jats:sub>\n                    ) and upregulates PD\u2010L1 expression on both tumor cells and T\n                    <jats:sub>EX<\/jats:sub>\n                    . Consequently, it is proposed that locally inhibiting T\n                    <jats:sub>EX<\/jats:sub>\n                    release is crucial for overcoming the adverse effects of mild PTT, thereby enhancing ICB therapy. Thus, a multi\u2010stage drug delivery system is designed that concurrently delivers photosensitizers (reduced graphene oxide nanosheets, NRGO), anti\u2010PD\u2010L1 antibodies, and exosome inhibitors (sulfisoxazole). The system employs a temperature\u2010sensitive lipid gel as the primary carrier, with NRGO serving as a secondary carrier that supports photothermal conversion and incorporation of sulfisoxazole. Importantly, controlled drug release is achieved using near\u2010infrared radiation. The findings indicate that this local combination therapy remodels the immunosuppressive TME through exosome inhibition and enhanced immune cell infiltration, while also boosting T\u2010cell activity to trigger systemic antitumor immunity, showcasing the remarkable efficacy of this combination strategy in eradicating cold tumors.\n                  <\/jats:p>","DOI":"10.1002\/advs.202406328","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T03:46:12Z","timestamp":1732247172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Local Exosome Inhibition Potentiates Mild Photothermal Immunotherapy Against Breast Cancer"],"prefix":"10.1002","volume":"12","author":[{"given":"Qian","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  639 Longmian Avenue Nanjing 211198 China"},{"name":"Department of 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