Selenium-Loaded Porous Silica Nanospheres Improve Cardiac Repair After Myocardial Infarction by Enhancing Antioxidant Activity and Mitophagy.

Abstract

Myocardial infarction (MI) is the leading cause of death globally, often resulting to significant loss of cardiac function. A key factor in the pathological progression of MI is the excessive generation of reactive oxygen species (ROS) by dysfunctional mitochondria. However, no antioxidant therapy has been approved for clinical treatment of MI to date. In this study, selenium-loaded porous silica nanospheres (Se@PSN) are synthesized as a novel therapeutic approach for MI. These nanospheres are capable of neutralizing various ROS, thereby reducing hypoxia-induced myocardial cell damage. Additionally, Se@PSN promote the upregulation of antioxidant proteins, providing sustained intracellular ROS scavenging, which helps reduce infarct size and preserve cardiac function post-MI. The sustained antioxidant effects of Se@PSN are attributed to their ability to safeguard mitochondrial function by modulating oxidative phosphorylation, mitochondrial dynamics, and mitophagy. The activation of mitophagy by Se@PSN is achieved through the upregulation of HIF-1α expression. In conclusion, Se@PSN show significant potential for clinical translation as a novel therapeutic strategy for MI.