Dapagliflozin-Loaded Exosome Mimetics Facilitate Diabetic Wound Healing by HIF-1α-Mediated Enhancement of Angiogenesis.

Abstract

Angiogenesis plays a critical role in diabetic wound healing. However, no effective strategies have been developed to target endothelial cells (ECs) to facilitate diabetic wound healing. Dapagliflozin (DA) as a sodium-glucose linked transporter 2 (SGLT2) inhibitor, may promote neovascularization in diabetic mice via HIF-1α-mediated enhancement of angiogenesis. Here, the bioinspired nanovesicles (NVs) prepared from induced pluripotent stem cells-derived ECs through an extrusion approach are reported, which can function as exosome mimetics to achieve targeted deliver of DA. Abundant membrane C-X-C motif chemokine receptor 4 conferred the EC-targeting ability of these NVs and the endothelial homology facilitated the accumulation in ECs. Furthermore, these DA-loaded induced pluripotent stem cells (iPSC)-EC NVs can facilitate angiogenesis and diabetic wound healing by HIF-1α/VEGFA pathway. Taken together, this study indicated that targeting ECs and regulating angiogenesis may be a promising strategy for the treatment of diabetic wound healing.