Issue 15, 2022

A glutathione-responsive sulfur dioxide polymer prodrug selectively induces ferroptosis in gastric cancer therapy

Abstract

Nanoparticle-induced ferroptosis has been proven to be an appealing strategy in cancer treatment. Previously, we reported the synthesis of an amphiphilic polymer prodrug of SO2, mPEG-PLG(DNs), which could self-assemble to formulate nanoparticles (NP-DNs) and trigger cancer cell death by GSH consumption and SO2 release. In the current study, the potential mechanism of NP-DNs-induced cell death was further investigated. We demonstrated that NP-DNs exhibited efficient antitumor activity against gastric cancer via ferroptosis. NP-DNs could selectively accelerate lipid peroxidation through GSH depletion and SO2 generation in gastric cancer cells. In addition, the NP-DNs-induced GPX4 reduction played a collaborative role in ferroptosis. Concurrently, in vivo evaluations revealed that NP-DNs not only exhibited excellent antitumor efficiency via ferroptosis but also caused little systemic toxicity in mice. All the results showed that NP-DNs would be a promising prodrug in precision-targeted ferroptosis therapy.

Graphical abstract: A glutathione-responsive sulfur dioxide polymer prodrug selectively induces ferroptosis in gastric cancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
02 May 2022
Accepted
08 Jun 2022
First published
09 Jun 2022

Biomater. Sci., 2022,10, 4184-4192

A glutathione-responsive sulfur dioxide polymer prodrug selectively induces ferroptosis in gastric cancer therapy

M. Xia, Z. Guo, X. Liu, Y. Wang and C. Xiao, Biomater. Sci., 2022, 10, 4184 DOI: 10.1039/D2BM00678B

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