Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Sci Bull (Beijing). 2023 Apr 30;68(8):826-837. doi: 10.1016/j.scib.2023.03.030. Epub 2023 Mar 21.
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, CX3CL1-functionalized 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.
内皮细胞 (EC) 损伤在慢性伤口过程中起着关键作用。长期的低氧微环境阻碍了 EC 的血管生成，从而延迟了伤口愈合。在这项研究中，构建了 CX3CL1 功能化凋亡体纳米囊泡 (nAB)。通过受体-配体结合实施“寻找-吞噬”策略，靶向在低氧微环境中高表达 CX3CR1 的 EC，从而放大“寻找-吞噬”信号，促进血管生成。通过化学诱导脂肪来源干细胞 (ADSCs) 凋亡获得凋亡体 (AB)，然后通过一系列步骤获得含有去铁胺 (DFO) 的功能性 nAB，包括优化的低渗处理、温和的超声、药物混合和挤出处理。体外实验表明，nAB 通过 CX3CL1/CX3CR1 具有良好的生物相容性和有效的“寻找-吞噬”信号，从而诱导低氧微环境中的 EC 增殖、迁移和管形成。体内实验表明，nAB 可促进伤口的快速闭合，释放“寻找-吞噬”信号以靶向 EC，并实现血管生成药物的持续释放，从而促进糖尿病伤口中新血管的形成。这些可以通过释放双重信号来靶向 EC 并实现血管生成药物持续释放的受体功能化 nAB，可能为慢性糖尿病伤口愈合提供一种新策略。
