Cardiac Dual‐Targeting Nanocatalysts for Heart Failure Therapy by Breaking the ROS–Inflammation Positive Feedback

Heart failure (HF) is a global public health challenge closely associated with oxidative stress and immune dysregulation. However, current therapeutic strategies for HF generally lack specific targeting to cardiac tissue, and the high perfusion rate of the heart further exacerbates insufficient drug accumulation at lesion sites, thus compromising therapeutic efficacy. Inspired by the barb-hook of Xanthium strumarium, Fe₃O₄@UiO-66 is functionalized with tannic acid (TA) to obtain a dual-target nanocatalyst, termed FUTA. In vitro, FUTA efficiently scavenges free radicals and eliminates superoxide anions and hydrogen peroxide through multiple enzyme-like activities, thus alleviating the isoproterenol (ISO)-induced increase in cellular reactive oxygen species (ROS) levels, restoring mitochondrial membrane potential, and alleviating pathological enlargement of cardiomyocytes. In vivo, FUTA accumulates selectively in injured myocardial tissue through external magnetic attraction and internal binding of TA to the cardiac extracellular matrix (ECM), exerting synergistic antioxidant and immunomodulatory effects, resulting in significant improvements in cardiac structure and function, as well as a reduction in fibrosis. These findings highlight the therapeutic potential of FUTA in alleviating myocardial injury through the coordinated regulation of metabolic and immune pathways, offering a promising material-based strategy for HF treatment.