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Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN\u2010micelle) with strong absorption in the second near infrared window (NIR\u2010II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR\u2010II SP sensors via a glutathione (GSH) responsive self\u2010immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature\u2010sensitive critical micelle concentration (CMC)\u2010switching method. Using this method, photothermal effect of SPRIN\u2010micelles in deep\u2010seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3\u2010dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T\u2010lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9\u00a0mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature\u2010sensitive F127 for the treatment of deep solid tumors.<\/jats:p>","DOI":"10.1002\/adhm.202303305","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T14:38:50Z","timestamp":1706279930000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep\u2010Seated Tumors"],"prefix":"10.1002","volume":"13","author":[{"given":"Gengqi","family":"Liu","sequence":"first","affiliation":[{"name":"School of Chemical Engineering and Technology Key Laboratory of Systems Bioengineering (Ministry of Education) Frontiers Science Center for Synthetic Biology (Ministry of Education) Tianjin University  Tianjin 300350 P. 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