Issue 26, 2024

Facile synthesis of a hydrazone-based zinc(ii) complex for ferroptosis-augmented sonodynamic therapy

Abstract

Sonodynamic therapy (SDT), as a novel non-invasive cancer treatment modality derived from photodynamic therapy (PDT), has drawn much attention due to its unique advantages for the treatment of deep tumors. Zinc-based complexes have shown great clinical prospect in PDT due to their excellent photodynamic activity and biosafety. However, their application in SDT has lagged seriously behind. Exploring efficient zinc-based complexes as sono-sensitizers remains an appealing but significantly challenging task. Herein, we develop a hydrazone ligand-based zinc complex (ZnAMTC) for SDT of tumors in vitro and in vivo. ZnAMTC was facilely synthesized via a two-step reaction from low-cost raw materials without tedious purification. It shows negligible dark toxicity and can produce singlet oxygen (1O2) under ultrasound (US) irradiation, exhibiting high sono-cytotoxicity to various cancer cells. Mechanism studies show that ZnAMTC can effectively reduce the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4) under US irradiation and later cause ferroptosis of cancer cells. In vivo studies further demonstrate that ZnAMTC exhibits efficient tumor growth inhibition under US irradiation and has good biosafety. This work provides useful insights into the design of first-row transition metal complexes for SDT application.

Graphical abstract: Facile synthesis of a hydrazone-based zinc(ii) complex for ferroptosis-augmented sonodynamic therapy

Supplementary files

Article information

Article type
Edge Article
Submitted
30 Mar 2024
Accepted
07 May 2024
First published
17 May 2024
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., 2024,15, 10027-10035

Facile synthesis of a hydrazone-based zinc(II) complex for ferroptosis-augmented sonodynamic therapy

D. Li, M. Fan, H. Wang, Y. Zhu, B. Yu, P. Zhang and H. Huang, Chem. Sci., 2024, 15, 10027 DOI: 10.1039/D4SC02102A

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