A glutathione-responsive sulfur dioxide polymer prodrug selectively induces ferroptosis in gastric cancer therapy. (21st June 2022)

• Record Type: Journal Article
• Authors: Xia, Mingjie; Guo, Zhihui; Liu, Xinming; Wang, Yang; Xiao, Chunsheng
• Is Part Of: Biomaterials science. Volume 10:Number 15(2022)
• Page Start: 4184
• Page End: 4192
• Publication Date: 2022-06-21
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d2bm00678b
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Glutathione-responsive sulfur dioxide polymer prodrug could consume glutathione and release SO2 to cooperatively elevate the intracellular ROS level, leading to selective induction of ferroptosis in gastric cancer cells. 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.