Abstract

Objective To develop a novel lipid nanoparticle (Ato@DSPE-PEG-CHP) for targeted delivery to ischemic myocardium to treat myocardial infarction.Methods Ato@DSPE-PEG-CHP was prepared using the thin-film dispersion method. Physicochemical properties were characterized by transmission electron microscope (TEM) and dynamic light scattering (DLS). In vitro targeting, uptake, and cytotoxicity were evaluated in OGD/R-treated HL-1 cells using confocal microscopy and CCK8. In vivo, a mouse MI model was established by ligating the left anterior descending coronary artery. The targeted distribution was observed using small animal in vivo imaging. Efficacy was evaluated using TTC, HE, Masson and TUNEL staining. Biosafety was evaluated through hemolysis assays and histopathological analysis.Results Ato@DSPE-PEG-CHP with uniform morphology, excellent dispersibility, and high stability were successfully prepared. This material can target myocardial ischemia sites both in vitro and in vivo. Ato@DSPE-PEG-CHP reduced infarct size, cell necrosis, inflammation, fibrosis, and apoptosis; decreased levels of tumor necrosis factor-α, interleukin-6, and malondialdehyde; and increased the enzyme activity of superoxide dismutase. Additionally, it demonstrated good biocompatibility and exhibited no significant toxicity to major organs.Conclusion Ato@DSPE-PEG-CHP specifically targeted ischemic myocardium, alleviated damage through its anti-inflammatory and antioxidant effects, and demonstrated superior efficacy and safety, presenting a promising treatment strategy for MI.