INSERM U1063, Université d'Angers, F-49000 Angers, France.
MitoLab, Unité MitoVasc, CNRS UMR 6015, INSERM U 1083, Université d'Angers, F-49000 Angers, France.
Nutrients. 2021 Dec 7;13(12):4378. doi: 10.3390/nu13124378.
(1) Background: The anthocyanin delphinidin exhibits anti-angiogenic properties both in in vitro and in vivo angiogenesis models. However, in vivo delphinidin is poorly absorbed, thus its modest bioavailability and stability reduce its anti-angiogenic effects. The present work takes advantage of small extracellular vesicle (sEV) properties to enhance both the stability and efficacy of delphinidin. When encapsulated in sEVs, delphinidin inhibits the different stages of angiogenesis on human aortic endothelial cells (HAoECs). (2) Methods: sEVs from immature dendritic cells were produced and loaded with delphinidin. A method based on UHPLC-HRMS was implemented to assess delphinidin metabolites within sEVs. Proliferation assay, nitric oxide (NO) production and Matrigel assay were evaluated in HAoECs. (3) Results: Delphinidine, 3-O-β-rutinoside and Peonidin-3-galactoside were found both in delphinidin and delphinidin-loaded sEVs. sEV-loaded delphinidin increased the potency of free delphinidin 2-fold for endothelial proliferation, 10-fold for endothelial NO production and 100-fold for capillary-like formation. Thus, sEV-loaded delphinidin exerts effects on the different steps of angiogenesis. (4) Conclusions: sEVs may be considered as a promising approach to deliver delphinidin to target angiogenesis-related diseases, including cancer and pathologies associated with excess vascularization.
(1) 背景：花色苷矢车菊素在体外和体内血管生成模型中均表现出抗血管生成特性。然而，体内矢车菊素的吸收能力较差，因此其适中的生物利用度和稳定性降低了其抗血管生成作用。本研究利用小细胞外囊泡（sEV）的特性来增强矢车菊素的稳定性和功效。当包裹在 sEV 中时，矢车菊素可抑制人主动脉内皮细胞（HAoECs）中不同阶段的血管生成。
(2) 方法：从小未成熟树突状细胞中产生 sEV 并加载矢车菊素。实施了一种基于 UHPLC-HRMS 的方法来评估 sEV 内矢车菊素的代谢物。在 HAoECs 中评估增殖测定、一氧化氮（NO）产生和 Matrigel 测定。
(3) 结果：在游离矢车菊素和加载矢车菊素的 sEV 中均发现了矢车菊定、3-O-β-芸香糖苷和矢车菊素-3-半乳糖苷。负载矢车菊素的 sEV 使游离矢车菊素对内皮细胞增殖的效力增加了 2 倍，对内皮细胞 NO 产生的效力增加了 10 倍，对毛细血管样形成的效力增加了 100 倍。因此，负载矢车菊素的 sEV 对血管生成的不同步骤都有作用。
(4) 结论：sEV 可被视为将矢车菊素递送至靶向与血管生成相关的疾病（包括癌症和与过度血管化相关的病理学）的有前途的方法。
