Ferroptosis Promotes Sonodynamic Therapy: A Platinum(II)-Indocyanine Sonosensitizer

Abstract

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, finally induces ferroptosis. In vivo studies further demonstrates that Pt-Cy inhibits tumor growth under US irradiation and its efficiency for SDT is better than that for PDT in vivo. 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.

Supplementary files

Article information

Article type
Edge Article
Submitted
10 May 2022
Accepted
02 Aug 2022
First published
05 Aug 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022, Accepted Manuscript

Ferroptosis Promotes Sonodynamic Therapy: A Platinum(II)-Indocyanine Sonosensitizer

Y. Lai, N. Lu, A. Ouyang, Q. Zhang and P. Zhang, Chem. Sci., 2022, Accepted Manuscript , DOI: 10.1039/D2SC02597C

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