Targeting exosome conjugated with cardiac homing peptide alleviates myocardial infarction by delivering miRNAs.

BACKGROUND: Conventional therapies for myocardial infarction (MI) have limited efficacy in restoring cardiac function. This study aimed to construct a novel engineered exosome platform for promoting post-MI cardiac regeneration and evaluate its therapeutic efficacy. METHODS: CCK-8 assays, flow cytometry, and western blotting were employed to evaluate the effects of DOPE-CHP-exosome on cardiomyocyte proliferation and apoptosis. The in vivo distribution of DOPE-CHP-exosome was assessed by fluorescence imaging, frozen sectioning, and DiI tracing. Cardiac function was evaluated using echocardiography, Masson's trichrome staining, and Sirius Red staining. RESULTS: The novel DOPE-CHP-exosome functionalized with cardiac homing peptide (CHP) and loaded with miR-126, miR-145, or miR-340-5p (DOPE-CHP-miR) enhanced exosome uptake by cardiomyocytes, improved cell viability, and reduced apoptosis in H2O2-induced primary cardiomyocyte injury models. In vivo, these exosomes markedly improved left ventricular contractility in MI mice, as evidenced by increased LVEF and LVFS and decreased LVEDV and LVESV. Additionally, the expression levels of CD31 and Ki67, markers of angiogenesis and proliferation, were significantly elevated. Notably, DOPE-CHP-miR-126 exhibited the most pronounced therapeutic effects. CONCLUSIONS: These DOPE-CHP-exosome alleviate MI and improve cardiac function by promoting cardiomyocyte viability and angiogenesis while inhibiting apoptosis.