Issue 2, 2024

An AIE-based monofunctional Pt(ii) complex for photodynamic therapy through synergism of necroptosis–ferroptosis

Abstract

Side effects and drug resistance are among the major problems of platinum-based anticancer chemotherapies. Photodynamic therapy could show improved tumor targeting ability and better anticancer effect by region-selective light irradiation. Here, we report an aggregation-induced emission (AIE)-based monofunctional Pt(II) complex (TTC-Pt), which shows enhanced singlet oxygen production by introduction of a Pt atom to elevate the intersystem crossing (ISC) rate. Moreover, TTC-Pt exhibits decent capacity of inhibition on tumor cell growth upon light irradiation, with negligible dark toxicity compared to the commonly used chemodrug cisplatin. Mechanistic study suggests that TTC-Pt enters HeLa cells via the endocytosis pathway and locates mainly in lysosomes, causing FSP1 down-regulation and intracellular lipid peroxidation accumulation under irradiation, finally leading to ferroptosis and necroptosis. The synergistic dual cell death pathways could help to kill apoptosis-resistant tumor cells. Therefore, TTC-Pt could serve as a potent antitumor photosensitizer, which overcomes the drug resistance with minimum side effects.

Graphical abstract: An AIE-based monofunctional Pt(ii) complex for photodynamic therapy through synergism of necroptosis–ferroptosis

Supplementary files

Article information

Article type
Paper
Submitted
30 jun 2023
Accepted
31 out 2023
First published
06 nov 2023
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2024,5, 141-147

An AIE-based monofunctional Pt(II) complex for photodynamic therapy through synergism of necroptosis–ferroptosis

X. Zheng, M. Liu, Y. Wu, Y. Chen, W. He and Z. Guo, RSC Chem. Biol., 2024, 5, 141 DOI: 10.1039/D3CB00113J

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