Tannin‐Mediated Ischemia‐Homing‐Angiogenesis Nanodots (IHAND) for Synergistic Angiogenesis and Heart Failure Prevention Post‐Myocardial Infarction

Insufficient angiogenic response in the early stage of myocardial infarction (MI) mediates the progression from MI to heart failure. The angiogenic response mainly involves two key cell types: vascular endothelial cells (VECs) and macrophages. However, current efforts to restore angiogenesis cannot achieve co-intervention of VECs and macrophages, which limits their clinical application. This study presents the first ischemia-homing-angiogenesis nanodots (IHAND) that simultaneously modulate VECs and macrophages to achieve efficient angiogenesis in MI tissues. IHAND is a potent composite antioxidant nanomedicine coated with tannic acid (TA) that can simultaneously achieve synergistic effects of repairing the tube-forming ability of VECs, promoting the secretion of angiogenic factors, and eliminating inflammatory factors. For the first time it is revealed that TA can specifically and strongly bind to the same CD31 ligand in VECs and macrophages. Accordingly, IHAND can target VECs and macrophages in MI tissues, alleviate proliferation and migration disorders of VECs, induce phenotypic transformation of macrophages in early stages of MI, significantly reduce the storm of inflammatory factors, and promote the secretion of vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor-BB (PDGF-BB). IHAND demonstrates strong angiogenic ability in MI, and its therapeutic effect is remarkably superior to that of N-acetylcysteine and canakinumab.