Find-eat strategy targeting endothelial cells via receptor functionalized apoptotic body nanovesicle

Endothelial cell (EC) injury plays a key role in the chronic wound process. A long-term hypoxic microenvironment hinders the vascularization of ECs, thus delaying wound healing. In this study, CX3CL1functionalized apoptotic body nanovesicles (nABs) were constructed. The Find-eat strategy was implemented through a receptor-ligand combination to target ECs that highly express CX3CR1 in the hypoxic microenvironment, therefore amplifying the Find-eat signal and promoting angiogenesis. Apoptotic bodies (ABs) were obtained by chemically inducing apoptosis of adipose-derived stem cells (ADSCs), and then functionalized nABs containing deferoxamine (DFO-nABs) were obtained through a series of steps, including optimized hypotonic treatment, mild ultrasound, drug mixing and extrusion treatment. In vitro experiments showed that nABs had good biocompatibility and an effective Find-eat signal via CX3CL1/CX3CR1 to induce ECs in the hypoxic microenvironment, thereby promoting cell proliferation, cell migration, and tube formation. In vivo experiments showed that nABs could promote the rapid closure of wounds, release the Find-eat signal to target ECs and realize the sustained release of angiogenic drugs to promote new blood vessel formation in diabetic wounds. These receptor-functionalized nABs, which can target ECs by releasing dual signals and achieve the sustained release of angiogenic drugs, may provide a novel strategy for chronic diabetic wound healing.(c) 2023 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.

Automated summary

In this study, CX3CL1-functionalized apoptotic body nanovesicles (nABs) were used to target endothelial cells (ECs) and promote angiogenesis in the chronic wound process. The Find-eat strategy was implemented to amplify the Find-eat signal and stimulate ECs in the hypoxic microenvironment. In vitro and in vivo experiments demonstrated that nABs had good biocompatibility, promoted wound closure, and released angiogenic drugs for new blood vessel formation in diabetic wounds. These receptor-functionalized nABs provide a novel strategy for chronic diabetic wound healing.