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The angiogenic response mainly involves two key cell types: vascular endothelial cells (VECs) and macrophages. However, current efforts to restore angiogenesis cannot achieve co\u2010intervention of VECs and macrophages, which limits their clinical application. This study presents the first ischemia\u2010homing\u2010angiogenesis 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\u2010forming 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\u2010A) and platelet\u2010derived growth factor\u2010BB (PDGF\u2010BB). IHAND demonstrates strong angiogenic ability in MI, and its therapeutic effect is remarkably superior to that of N\u2010acetylcysteine and canakinumab.<\/jats:p>","DOI":"10.1002\/adma.202514662","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:42:46Z","timestamp":1762764166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Tannin\u2010Mediated Ischemia\u2010Homing\u2010Angiogenesis Nanodots (IHAND) for Synergistic Angiogenesis and Heart Failure Prevention Post\u2010Myocardial Infarction"],"prefix":"10.1002","volume":"38","author":[{"given":"Xiaohui","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Cardiology The Third Xiangya Hospital Central South University  Changsha Hunan 410000 P. R. China"},{"name":"Department of Cardiology Xiangya Hospital Central South University  Changsha Hunan 410000 P. R. 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