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However, as a factor that mediates tumor metastasis and immune suppression, the impact of tumor exosomes on therapy under electromagnetic energy stimulation remains unclear. Herein, findings indicate that sonodynamic therapy (SDT) increases serum exosome levels by inducing apoptotic exosomes and loosening the tumor extracellular matrix, promoting lung metastasis. To address this problem, an exosome\u2010inhibiting polymeric sonosensitizer (EIPS) selectively inhibiting tumor exosome generation in response to the tumor biomarker is synthesized. EIPS consists of a semiconducting polymer backbone capable of inducing SDT and a poly(ethylene glycol) layer conjugated with a tumor\u2010specific enzyme\u2010responsive exosome inhibitor prodrug. After being cleaved by tumor Cathepsin B, EIPS releases active exosome inhibitors, preventing tumor exosome\u2010mediated immune suppression and lung metastasis. As a result, EIPS elicits robust antitumor effects through the synergistic effect of SDT and tumor exosome inhibition, completely preventing lung metastasis and establishing a long\u2010term immune memory effect. This is the first example showing that combining SDT with tumor\u2010specific exosome inhibition can elicit a potent immune response without the help of typical immune agonists.<\/jats:p>","DOI":"10.1002\/adma.202400762","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T05:53:57Z","timestamp":1709704437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Exosome\u2010Inhibiting Polymeric Sonosensitizer for Tumor\u2010Specific Sonodynamic Immunotherapy"],"prefix":"10.1002","volume":"36","author":[{"given":"Jiayan","family":"Wu","sequence":"first","affiliation":[{"name":"School of Chemistry, Chemical Engineering and Biotechnology Nanyang Technological University  Singapore 637457 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsheng","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chemistry, Chemical Engineering and 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