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Sono\u2010activatable semiconducting polymer nanoreshapers (SPN<jats:sub>DN<\/jats:sub>H) are constructed to multiply remodel tumor microenvironment of orthotopic pancreatic cancer for potent immunotherapy. SPN<jats:sub>DN<\/jats:sub>H contain a semiconducting polymer, hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) donor, and indoleamine 2,3\u2010dioxygenase (IDO) inhibitor (NLG919), which are encapsulated by singlet oxygen (<jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub>)\u2010responsive shells with modification of hyaluronidase (HAase). After accumulation in orthotopic pancreatic tumor sites, SPN<jats:sub>DN<\/jats:sub>H degrade the major content of tumor microenvironment hyaluronic acid to promote nanoparticle enrichment and immune cell infiltration, and also release H<jats:sub>2<\/jats:sub>S to relieve tumor hypoxia via inhibiting mitochondrion functions. Moreover, the relieved hypoxia enables amplified sonodynamic therapy (SDT) under ultrasound (US) irradiation with generation of <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub>, which leads to immunogenic cell death (ICD) and destruction of <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub>\u2010responsive components to realize sono\u2010activatable NLG919 release for reversing IDO\u2010based immunosuppression. Through such a multiple remodeling mechanism, a potent antitumor immunological effect is triggered after SPN<jats:sub>DN<\/jats:sub>H\u2010based treatment. Therefore, the growths of orthotopic pancreatic tumors in mouse models are almost inhibited and tumor metastases are effectively restricted. This study offers a sono\u2010activatable nanoplatform to multiply remodel tumor microenvironment for effective and precise immunotherapy of deep\u2010tissue orthotopic tumors.<\/jats:p>","DOI":"10.1002\/advs.202305150","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T07:49:59Z","timestamp":1698047399000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Sono\u2010Activatable Semiconducting Polymer Nanoreshapers Multiply Remodel Tumor Microenvironment for Potent Immunotherapy of Orthotopic Pancreatic Cancer"],"prefix":"10.1002","volume":"10","author":[{"given":"Meng","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Biological Science and Medical Engineering Donghua University  Shanghai 201620 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