肿瘤细胞治疗研究
英文原题：Desialylated Mesenchymal Stem Cells-Derived Extracellular Vesicles Loaded with Doxorubicin for Targeted Inhibition of Hepatocellular Carcinoma.
Desialylated Mesenchymal Stem Cells-Derived Extracellular Vesicles Loaded with Doxorubicin for Targeted Inhibition of Hepatocellular Carcinoma.
本研究使用去唾液酸化MSC-EVs的递送系统的结果提示其用于HCC的治疗潜力。
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。HCC患者的治疗方案多种多样，但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）来源的细胞外囊泡（EVs）负载多柔比星（Dox）的递送系统。在该系统中，我们首先通过神经氨酸酶去除了EVs表面的末端连接2-3和2-6唾液酸。处理后的MSC-EVs中半乳糖（Gal）和N-乙酰半乳糖胺（GalNAc）残基的表达可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显著表现出改善的细胞摄取、优先的靶向效力，并在体外和体内具有更好的抑制效果。总体而言，本研究结果所展示的使用去唾液酸化MSC-EVs的递送系统表明其具有治疗HCC的潜力。
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 2-3 and 2-6 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.
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