Targeted and Infarcted Microenvironment‐Responsive Peptide Therapeutics to Reverse Cardiac Remodeling

Abstract Acute myocardial infarction (AMI) leads to cardiac remodeling and heart failure ultimately. However, the present therapeutic approaches show limited effects on restoring the blood supply quickly and controlling cardiac remodeling effectively. Here, a novel strategy for the repair of the injured heart by using tannic acid (TA) to deliver the therapeutic Neuropeptide Y (NPY), which is bio‐responsively released by the incorporation of matrix metalloproteinase cleavable peptide Pro‐Leu‐Gly‐Leu‐Ala‐Gly (TIMP), is developed. The NPY‐loaded nanostructure, designated as TNT (TA/NPY/TIMP), is evaluated for its therapeutic effects on cardiac remodeling after AMI in mice. TNT specifically targets to infarcted tissues and releases NPY in the AMI environment with abundant matrix metalloproteinase 2. Interestingly, it is found that TNT attenuates early post‐MI cardiac remodeling via increasing angiogenesis and the transition of M1 macrophages to M2 phenotype. This work contributes to developing a novel strategy for the recovery of cardiac functions after AMI.