Platelet-mimicking nanoparticles loaded with diallyl trisulfide for Mitigating Myocardial Ischemia‐Reperfusion Injury in rats

Hydrogen sulfide (H 2 S) shows promise in treating myocardial ischemia-reperfusion injury (MIRI), but the challenge of controlled and sustained release hinders its clinical utility. In this study, we developed a platelet membrane-encapsulated mesoporous silica nanoparticle loaded with the H 2 S donor diallyl trisulfide (PM-MSN-DATS). PM-MSN-DATS demonstrated optimal encapsulation efficiency and drug-loading content. Comprehensive in vitro and in vivo assessments confirmed the biosafety of PM-MSN-DATS. In vitro, PM-MSN-DATS adhered to inflammation-activated endothelial cells and exhibited targeted accumulation in MIRI rat hearts. In vivo experiments revealed significant reductions in reactive oxygen species (ROS) and myocardial fibrosis area, improving cardiac function. Our findings highlight successfully creating a targeted H 2 S delivery system through platelet membrane-coated MSN nanoparticles. This well-designed drug delivery platform holds significant promise for advancing MIRI treatment strategies. Schematic illustration of biomimetic nanoparticles for targeted delivery of DATS and localized release of H 2 S to attenuate MIRI. • Hydrogen sulfide has displayed promising therapeutic potential in addressing myocardial ischemia-reperfusion injury. • The controlled and sustained release of hydrogen sulfide remains a critical challenge. • Platelet membrane-coated mesoporous silica nanoparticles loaded with the diallyl trisulfide were successfully developed. • These nanoparticles can selectively aggregate and release hydrogen sulfide in the locally damaged myocardium. • Our study provided a novel targeted delivery strategy for gas therapy in myocardial ischemia-reperfusion injury.