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<p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年5月5日

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  • Farshid Jaberi Ansari,
  • Javad Behroozi,
  • Mohsen Chamanara,
  • Mostafa Shahrezaee,
  • Ali Shakerimoghaddam,
  • Seyed Hossein Mousavi,
  • Amir Amanzadeh,
  • Mohammad Ali Shokrgozar,
  • Hossein Ahmadi Tafti,
  • Mahdi Ghorbani,
  • David W. Greening,
  • Reza Heidari

摘要

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.

Graphical Abstract