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Strategies for precise spatiotemporal activation of antitumor immunity can tackle these issues but remain challenging. Herein, a semiconducting polymeric nanoagonist (SPNM) with in situ sono\u2010activatable immunotherapeutic effects for precision sono\u2010immunotherapy of HNSCC is reported. SPNM is self\u2010assembled from a sonodynamic semiconducting polymer core conjugated with a stimulator of interferon genes (STING) agonist (MSA\u20102) via a singlet oxygen cleavable linker. Under sono\u2010irradiation, SPNM produces singlet oxygen not only to eradicate tumor cells to trigger immunogenic cell death but also to unleash caged STING agonists via the cleavage of diphenoxyethene bonds for in situ activation of the STING pathway in the tumor region. Such sono\u2010driven STING activation mediated by SPNM promotes effector T cell infiltration and potentiates systemic antitumor immunity, eventually leading to tumor growth inhibition and long\u2010term immunological memory. This study thus presents a promising strategy for the precise spatiotemporal activation of cancer immunotherapy.<\/jats:p>","DOI":"10.1002\/adma.202300854","type":"journal-article","created":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T07:15:02Z","timestamp":1682752502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Sono\u2010Driven STING Activation using Semiconducting Polymeric Nanoagonists for Precision Sono\u2010Immunotherapy of Head and Neck Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"35","author":[{"given":"Jianli","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Chemistry &amp; Chemical Engineering Nanjing University Nanjing 210023 P. R. 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