Ferroptosis 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 (O) 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. studies further demonstrate that Pt-Cy inhibits tumor growth under US irradiation and its efficiency for SDT is better than that for PDT . This is the first example of platinum(ii) complexes for sonodynamic therapy. This work extends the biological applications of metal complexes from PDT to SDT.