Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an 710069, China.
Institute of Hematology, School of Medicine, Northwest University, Xi'an 710069, China.
Cells. 2022 Aug 25;11(17):2642. doi: 10.3390/cells11172642.
Hepatocellular carcinoma (HCC) is one of the dominating causes of cancer-related death throughout the world. Treatment options for patients with HCC vary, however, the lack of effective targeted drugs is the major reason for death in advanced HCC patients. In this study, a delivery system based on mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) loaded with doxorubicin (Dox) was developed. In this system, we initially erased terminal linked α2-3 and α2-6 sialic acids on the surface of EVs by neuraminidase. The exhibition of galactose (Gal) and N-acetylgalactosamine (GalNAc) residues in treated MSC-EVs can specifically be recognized by asialoglycoprotein receptor (ASGPR) of hepatoma cells. Compared to free Dox and Dox-loaded EVs, desialylated EVs loaded with Dox significantly presented the improved cellular uptake, prioritized targeting efficacy, and had a better inhibiting effect in vitro and in vivo. Overall, the results of the present study of the demonstrated delivery system using desialylated MSC-EVs suggest its therapeutic potential for HCC.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。然而，HCC 患者的治疗选择因个体而异，缺乏有效的靶向药物是晚期 HCC 患者死亡的主要原因。在本研究中，开发了一种基于间充质干细胞（MSC）衍生的外泌体（EVs）负载多柔比星（Dox）的递送系统。在该系统中，我们最初通过神经氨酸酶去除 EVs 表面末端连接的α2-3 和 α2-6 唾液酸。经过处理的 MSC-EVs 中展示的半乳糖（Gal）和 N-乙酰半乳糖胺（GalNAc）残基可以被肝癌细胞的去唾液酸糖蛋白受体（ASGPR）特异性识别。与游离 Dox 和负载 Dox 的 EVs 相比，负载 Dox 的去唾液酸化 EVs 显著提高了细胞摄取率，优先靶向效果，并在体外和体内具有更好的抑制作用。总之，本研究中使用去唾液酸化 MSC-EVs 的递药系统的结果表明其在 HCC 治疗方面具有潜在的应用价值。
