Selenotrisulfide delivery restores redox balance in myocardial infarction via a thiol-exchange reaction <i>in situ</i>.

Li, Shifen; Wang, Beiduo; Zheng, Weiwei; Hu, Xinman; Shen, Liyin; Deng, Jun; Zhu, Yang; Liu, Wenxing et al. · Bioact Mater · 2026

basic_science · Level V

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Abstract

The enzyme activity of redox-related selenoproteins is impaired post-tissue injury or inflammation, exacerbating oxidative stress and apoptosis. In this study, we present a strategy using selenotrisulfide (STS) to enhance the selenium content and restore selenoprotein-like activity <i>in vivo</i> via thiol-exchange reactions. The exact mass-to-charge ratio (<i>m</i>/<i>z</i>) change was observed at cysteine residue sites by liquid chromatography-mass spectroscopy (LC-MS), demonstrating the feasibility of the thiol-exchange reaction and the modification of selenium with proteins. Compared to the traditional selenium sources such as sodium selenite (Na<sub>2</sub>SeO<sub>3</sub>), L-selenomethionine (SeMet) and L-selenocysteine ((Sec)<sub>2</sub>), STS exhibited superior antioxidative and therapeutic efficacy by augmenting selenium levels and oxidoreductase-like activities <i>in vitro</i> and in <i>vivo</i>. Proteomic analysis revealed that STS could better improve myocardial contraction and regulate glucolipid metabolism to enhance energy supply and cardiac repair. Furthermore, the core-shell nanofibrous ZPB@STS patch significantly contributed to lower inflammatory response, less cell death and collagen deposition, and stronger cardiac contraction through the cooperative interaction of selenium-regulation from STS and mechanical support from the elastomeric polyurethane fibrous patch.