A mitochondria-targeted nanomedicine for myocardial ischemia/reperfusion injury with synergistic antioxidant and anti-inflammatory properties
Congcong Li, Zhengfeng Zhang, Chao Luo, Wanqi Lan, Chen Liu, Wu Liu, Haiyan Xiang, Juesheng Yang, Yanhua Tang, Xiaolei Wang
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.