A mitochondria-targeted nanomedicine for myocardial ischemia/reperfusion injury with synergistic antioxidant and anti-inflammatory properties

Abstract

Acute myocardial infarction (AMI) remains the leading cause of mortality worldwide, posing a significant threat to global public health. Although revascularization strategies such as percutaneous coronary intervention represent the standard treatment for AMI, myocardial cell death caused by myocardial ischemia/reperfusion injury (MI/RI) significantly compromises clinical efficacy. The clinical application of anti-inflammatory and antioxidant therapeutic medicine for MI/RI is hindered by critical limitations, including poor targeting and low bioavailability. A novel mitochondria-targeted nanomedicine, VB@MOF/TA, was successfully constructed, utilizing a metal-organic framework (MOF) as a carrier to achieve synergistically antioxidant and anti-inflammatory activities of verbascoside (VB), and employing a tannic acid (TA)-based nanocomplex for specific mitochondrial localization. Cellular experiments demonstrate that VB@MOF/TA co-localizes with mitochondria, exerts potent antioxidant effects, significantly suppresses oxygen-glucose deprivation/reoxygenation-induced cardiomyocyte apoptosis, and effectively modulates macrophage polarization. In vivo studies confirm that, compared with VB monotherapy, the VB@MOF/TA group exhibits a 2.59-fold reduction in apoptosis rate, a 7.72% ± 3.71% improvement in left ventricular ejection fraction, and a 2.50-fold increase in vascular density. These findings indicate that VB@MOF/TA significantly mitigates MI/RI and promotes myocardial tissue remodeling through its targeted antioxidant and synergistic anti-inflammatory mechanisms, highlighting its substantial clinical translational potential.