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By harnessing ultrasound waves in tandem with sonosensitizers, this method produces reactive oxygen species (ROS) that inflict oxidative damage upon tumor cells, subsequently causing their demise. Ferroptosis is a regulatory form of cell death that differs from other forms, characterized by iron accumulation, ROS accumulation, and lipid peroxidation. In the presented research, a nanoparticle formulation, parthenolide\/ICG\u2010CaCO<jats:sub>3<\/jats:sub>@lipid (PTL\/ICG\u2010CaCO<jats:sub>3<\/jats:sub>@Lip), has been engineered to amplify ferroptosis in tumor cells, positioning it as a potent agent for sonodynamic cancer immunotherapy. This nanoparticle significantly augments ROS levels within tumor cells, inducing oxidative stress that leads to cell death. The therapeutic potential of PTL\/ICG\u2010CaCO<jats:sub>3<\/jats:sub>@Lip, both in vivo and in vitro, has been convincingly demonstrated. Furthermore, RNA\u2010seq analysis insights revealed that PTL\/ICG\u2010CaCO<jats:sub>3<\/jats:sub>@Lip facilitates tumor cell ferroptosis by regulating P53 to downregulate SLC7A11 protein expression, thereby inhibiting the glutamate\u2010cystine antiporter system Xc<jats:sup>\u2212<\/jats:sup> and stimulating ACSL4\/LPCAT3 pathways. This pioneering work uncovers an innovative strategy for combatting tumors, leveraging enhanced oxidative stress to promote cell ferroptosis, and paves the way for groundbreaking cancer immunotherapeutic interventions.<\/jats:p>","DOI":"10.1002\/exp.20240002","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T13:17:15Z","timestamp":1719407835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["A pH responsive nanocomposite for combination sonodynamic\u2010immunotherapy with ferroptosis and calcium ion overload via SLC7A11\/ACSL4\/LPCAT3 pathway"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4103-5501","authenticated-orcid":false,"given":"Xue","family":"Bai","sequence":"first","affiliation":[{"name":"School of Life Sciences Tianjin University  Tianjin China"},{"name":"Tianjin Key Laboratory of Function and Application of Biological 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