Nanocatalytic antioxidation synergizes cardioprotection and antifibrosis in cardiac injury

Abstract

Myocardial injury and fibrosis are two important features of acute cardiac ischemia, both lead to heart failure. Clinical data indicate that targeting myocardial injury or fibrosis alone are not sufficient to improve myocardial infraction patient prognosis. Notably, reactive oxygen species (ROS) play a critical role in both myocardial injury and fibrosis, through disrupting redox homeostasis within cardiomyocytes, and mediating profibrotic signaling within fibroblasts as well. Herein, a nanocatalytic antioxidative therapeutic methodology is developed for synergistic treatment of post-ischemic cardiac injury, by using zeolitic imidazolate framework-67 nanoparticles (ZIF-67 NPs) as paradigmatic antioxidative nanocatalysts, to efficiently scavenge ROS for concurrent cardioprotection and antifibrosis. ZIF-67 NPs are capable of efficiently catalyzing hydrogen peroxide disproportionation owing to the enriched Co-N₄ active sites, which can restore redox homeostasis in cardiomyocytes to inhibit apoptosis/ferroptosis. More intriguingly, the catalytic ROS-scavenging effect can further suppress redox signaling within fibroblasts to inhibit their transition to myofibroblast. In vivo results further demonstrate the significant efficacy of nanocatalytic antioxidation for cardioprotection and antifibrosis. This study provides a feasible approach for synergistic treatment of post-ischemic cardiac injury by nanocatalytic antioxidation.