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Although sonodynamic therapy (SDT) offers a non\u2010invasive approach with deep tissue penetration, its effectiveness using wide\u2010bandgap sonosensitizers is constrained by rapid electron\u2010hole recombination. Guided by AI\u2010driven screening, we developed narrow\u2010bandgap (1.0\u20131.5\u00a0eV) tin monosulfide (SnS) as a sonosensitizer, which was further engineered into a cascade reaction\u2010enhanced sonodynamic therapeutic system by loading nitric oxide (NO) donors and modifying with polyethylene glycol (PEG). Upon ultrasound stimulus, this system generates both ROS and NO, which not only exert the cytotoxic effects of sonodynamic therapy but also combine to yield highly cytotoxic peroxynitrite (ONOO\n                    <jats:sup>\u2212<\/jats:sup>\n                    ). The resulting ONOO\n                    <jats:sup>\u2212<\/jats:sup>\n                    activates matrix metalloproteinases (MMPs) to degrade the ECM, thereby enhancing nanoparticle penetration and establishing a self\u2010reinforcing antitumor cycle. Furthermore, this ultrasound\u2010driven strategy simultaneously induces mitochondrial apoptosis via ROS, overcoming the depth limitations of conventional light\u2010based therapies and presenting a potent approach for TNBC treatment.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202505513","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:40:33Z","timestamp":1772966433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ultrasound\u2010Triggered Peroxynitrite\u2010Mediated ECM Degradation to Enhance Sonodynamic Cancer Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Jing","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE)&amp; Institute of Advanced Materials (IAM) School of Flexible Electronics (Future Technologies) Nanjing Tech University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyan","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE)&amp; Institute of Advanced Materials (IAM) School of Flexible Electronics (Future Technologies) Nanjing Tech University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Si","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE)&amp; Institute of Advanced Materials (IAM) School of Flexible Electronics (Future Technologies) Nanjing Tech University  Nanjing China"},{"name":"State Key Laboratory of Molecular Engineering of Polymers Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE)&amp; Institute of Advanced Materials (IAM) School of Flexible Electronics (Future Technologies) Nanjing Tech University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzhen","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE)&amp; Institute of Advanced Materials (IAM) School of Flexible Electronics (Future Technologies) Nanjing Tech University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE)&amp; Institute of Advanced Materials (IAM) School of Flexible Electronics (Future Technologies) Nanjing Tech University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiguang","family":"Han","sequence":"additional","affiliation":[{"name":"School of Chemistry &amp;\u00b7Materials\u00b7Science Jiangsu Normal University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7327-8060","authenticated-orcid":false,"given":"Xiaochen","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Flexible Electronics (LoFE)&amp; Institute of Advanced Materials (IAM) School of Flexible Electronics (Future Technologies) Nanjing Tech University  Nanjing China"},{"name":"School of Chemistry &amp;\u00b7Materials\u00b7Science Jiangsu Normal University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.12.017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CS00648F"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5RA01501D"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202300234"},{"key":"e_1_2_10_6_1","article-title":"Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model","volume":"157","author":"Cheng R. 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