Selenotrisulfide delivery restores redox balance in myocardial infarction via a thiol-exchange reaction in situ

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 in vivo via thiol-exchange reactions. The exact mass-to-charge ratio ( m / z ) 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 2 SeO 3 ), L-selenomethionine (SeMet) and L-selenocysteine ((Sec) 2 ), STS exhibited superior antioxidative and therapeutic efficacy by augmenting selenium levels and oxidoreductase-like activities in vitro and in vivo . 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. Thiol-change reaction is employed to increase the local selenium content and modulate the selenoproteins-like activity. The innovative selenium supplement (Pen-S-Se-S-Pen, STS) reacts with proteins at the cysteine residues (-SH) in vivo , enhancing anti-oxidation ability and achieving promising therapy for myocardial infarction. • A selenium supplement (STS) reacted with proteins by the thiol-exchange reaction to form new selenium active sites. • STS enhanced better localized selenium level and modulated selenoprotein-like activity. • STS could better improve myocardial contraction and regulate the glucolipid metabolism process to enhance cardiac repair.