biostudies-literatureUnknown13(34)Lai YSonodynamic therapy (SDT) has unique advantages in deep tumour ablation due to its deep penetration depth, showing great preclinical and clinical potential. Herein, a platinum(ii)-cyanine complex has been designed to investigate its potential as a SDT anticancer agent. It generates singlet oxygen (¹O₂) under ultrasound (US) irradiation or light irradiation, and exhibits US-cytotoxicity in breast cancer 4T1 cells but with negligible dark-cytotoxicity. Mechanistic investigations reveal that Pt-Cy reduces the cellular GSH and GPX4, and triggers cancer cell ferroptosis under US irradiation. The metabolomics analysis illustrates that Pt-Cy upon US treatment significantly dysregulates glutathione metabolism, and finally induces ferroptosis. <i>In vivo</i> studies further deChemical science9921-9926https://www.ebi.ac.uk/biostudies/studies/S-EPMC9430585biostudies-literatureFerroptosis promotes sonodynamic therapy: a platinum(ii)-indocyanine sonosensitizer.PMC9430585Lai YOuyang ALu NZhang QZhang PfalseFerroptosis promotes sonodynamic therapy: a platinum(ii)-indocyanine sonosensitizer.Sonodynamic therapy (SDT) has unique advantages in deep tumour ablation due to its deep penetration depth, showing great preclinical and clinical potential. Herein, a platinum(ii)-cyanine complex has been designed to investigate its potential as a SDT anticancer agent. It generates singlet oxygen (¹O₂) under ultrasound (US) irradiation or light irradiation, and exhibits US-cytotoxicity in breast cancer 4T1 cells but with negligible dark-cytotoxicity. Mechanistic investigations reveal that Pt-Cy reduces the cellular GSH and GPX4, and triggers cancer cell ferroptosis under US irradiation. The metabolomics analysis illustrates that Pt-Cy upon US treatment significantly dysregulates glutathione metabolism, and finally induces ferroptosis. <i>In vivo</i> studies further de2022-01-01T00:00:00Z2022 Aug2025-04-26T13:51:33.217Z2024-11-14T20:10:43.857ZS-EPMC94305853612823010.1039/d2sc02597c