Engineered ATP-Loaded Extracellular Vesicles: A Dual-Functional Strategy for Improving Myocardial Infarction Therapy

Myocardial infarction (MI) is a major component of cardiovascular disease. The primary challenge in MI therapy is the lack of energy in the affected tissue. Extracellular vesicles (EVs) areengineered with adenosine triphosphate (ATP) and targeted with an anti-myosin antibody (T-EV) to effectively deliver energy to damaged myocardial tissue and mitigate the effects of myocardial infarction (MI). Furthermore, using an in vivo MI rat model to evaluate cardiac repair, we compared cardiac function, infarct size, and the expression of troponin and α-actin four weeks after MI with those in a healthy group. The results indicate that, compared with no treatment, the use of Target-ATP-EVs (T-ATP-EVs) enhances the viability of hypoxic cells by 46% and reduces apoptosis by 28%. In the animal study, there was a 26% increase in the left ventricular ejection fraction (LVEF) and a 28% decrease in the infarct size compared with those of the MI group when this treatment was applied. Additionally, the expression levels of troponin and α-actin increased approximately two-fold in vivo with the use of these engineered EVs. In this study, engineered EVs were investigated as a strategy to deliver ATP directly to cardiomyocytes and heart tissue in both in vitro and in vivo models. The system described here enhances cardiomyocyte survival and function, marking a significant advancement in the treatment of myocardial infarction.