Heart-homed nanomedicine induces fast mitochondrial rescue to enhance cardiac function post-myocardial infarction.

Abstract

In myocardial infarction (MI), mitochondrial dysfunction acts as a core mechanism linking energy failure to multiple downstream pathological processes, ultimately determining cardiomyocyte fate and cardiac function. However, the rapid and safe restoration of cardiomyocyte mitochondrial function remains a major challenge in MI therapy. Herein, we present a heart-homed fast acting mitochondrial-function enhancer (H-FAME), rationally engineered to achieve sequential targeting from ischemic myocardial tissue to cardiomyocyte mitochondria. By synergistically modulating mitochondrial membrane potential (MMP) and oxidative stress, H-FAME stabilizes mitochondrial function, thereby attenuating cardiomyocyte loss, inflammation, and fibrosis and ultimately promoting functional recovery after MI. In summary, H-FAME provides a robust approach for energy homeostasis restoration, and lays the foundation for the development of related mitochondrial protective drugs to treat MI.