Abstract
The excessive release of reactive oxygen species (ROS) after myocardial infarction (MI) disrupts the natural healing process, leading to cardiac fibrosis and compromising patient prognosis. However, the clinical application of many antioxidant drugs for MI treatment is hindered by their poor antioxidant efficacy and inability to specifically target the heart. Here we developed a tannic acid-modified MnO(2) nanozyme (named MnO(2)@TA), which can achieve cardiac targeting to inhibit post-MI fibrosis and enhance cardiac function. Specifically, the MnO(2)@TA nanozyme, endowed with superoxide dismutase (SOD) and catalase (CAT) activities, effectively scavenges ROS, suppressing fibroblast activation and mitigating cardiac fibrosis without affecting cardiac repair. Notably, the incorporation of TA improves the nanozyme's affinity for the elastin and collagen-rich extracellular matrix in cardiac tissues, significantly increasing its retention and uptake within the heart and thereby enhancing its anti-fibrotic efficacy. In a murine myocardial infarction model, MnO(2)@TA demonstrates remarkable cardiac protection and safety, significantly improving cardiac function while attenuating cardiac fibrosis. This study presents a valuable reference for clinical research aimed at inhibiting cardiac fibrosis and advancing myocardial infarction treatments.