Engineered ATP-loaded extracellular vesicles: a dual-functional strategy for improving myocardial infarction therapy.

Abstract

Myocardial infarction (MI) represents a major component of cardiovascular disease, primarily due to severe energy depletion in ischemic tissue. Extracellular vesicles (EVs) have recently emerged as promising cell-free nanocarriers capable of targeted delivery and intercellular communication. Leveraging these advantages, engineered EVs were investigated in this study as a direct ATP-delivery platform to cardiomyocytes. EVs were functionalized with an anti-myosin antibody to form targeted extracellular vesicles (T-EVs) and subsequently loaded with ATP, generating T-ATP-EVs for selective energy transfer to damaged myocardium. We study viability and apoptosis of ischemia cells by alamar Blue and flowcytometry (annexin-PI) under hypoxic condition in vitro also we use cardiac function, infarct size, and the expression of troponin and α-actin four weeks after MI on MI rat model in vivo for assessment cardiac repair. The results indicate that, compared with no treatment, the use of T-ATP-EVs enhances the viability of hypoxic cells by 46% and reduces apoptosis by 40%. In the animal study, T-ATP-EVs group increase 27% left ventricular ejection fraction (LVEF) also infarct size decrese 28% compared with control group. Additionally, the expression levels of troponin and α-actin increased approximately two-fold when we use T-ATP-EVs in vivo. In this study, T-ATP-EVs were investigated as a strategy to deliver ATP directly to cardiomyocytes and heart tissue . The system described here enhances cardiomyocyte survival and targeting damaged heart tissue which making a significant advancement in the treatment of MI.