A “drug-carrier homologation” cardiac patch for myocardial infarction therapy via month-long controlled H2S release

Abstract

Hydrogen sulfide (H2S), a gaseous signaling molecule with multiple cardioprotective effects, has attracted considerable attention for treating myocardial infarction (MI), a leading global cause of death. However, its ultrashort half-life (seconds to minutes) and the extended recovery required for myocardial repair pose substantial challenges to therapeutic efficiency, emphasizing the urgent need for month-level controlled H2S delivery strategies, an endeavor still unresolved. Inspired by natural trisulfide H2S donors, we introduce a novel disulfide/trisulfide cross-linked network derived from natural lipoic acid (LA) and its trisulfide derivative LATS, engineered as a drug-carrier homologated cardiac patch (Fe@LA/LATS) for MI therapy. Fe@LA/LATS adheres firmly to wet cardiac tissue, providing stable mechanical support while undergoing thiol-responsive depolymerization to release LA and H2S. In situ-released LA scavenges reactive oxygen species (ROS) and attenuates the inflammatory response around the infarcted myocardium. Concurrently, H2S significantly stimulates cardiomyocyte proliferation and angiogenesis, further accelerating myocardial regeneration and functional recovery. Impressively, Fe@LA/LATS containing 5% LATS ensures a controlled release of H2S at therapeutically effective levels for 1 month, with a seamless release process until complete degradation. This new strategy dramatically enhances the overall therapeutic efficiency, holding promising potential for further applications.