A Cardiac‐Targeted Nanozyme Interrupts the Inflammation‐Free Radical Cycle in Myocardial Infarction

Abstract Severe systemic inflammation following myocardial infarction (MI) is a major cause of patient mortality. MI‐induced inflammation can trigger the production of free radicals, which in turn ultimately leads to increased inflammation in cardiac lesions (i.e., inflammation‐free radicals cycle), resulting in heart failure and patient death. However, currently available anti‐inflammatory drugs have limited efficacy due to their weak anti‐inflammatory effect and poor accumulation at the cardiac site. Herein, a novel Fe‐Cur@TA nanozyme is developed for targeted therapy of MI, which is generated by coordinating Fe 3+ and anti‐inflammatory drug curcumin (Cur) with further modification of tannic acid (TA). Such Fe‐Cur@TA nanozyme exhibits excellent free radicals scavenging and anti‐inflammatory properties by reducing immune cell infiltration, promoting macrophage polarization toward the M2‐like phenotype, suppressing inflammatory cytokine secretion, and blocking the inflammatory free radicals cycle. Furthermore, due to the high affinity of TA for cardiac tissue, Fe‐Cur@TA shows an almost tenfold greater in cardiac retention and uptake than Fe‐Cur. In mouse and preclinical beagle dog MI models, Fe‐Cur@TA nanozyme preserves cardiac function and reduces scar size, suggesting promising potential for clinical translation in cardiovascular disease.