Desialylated Mesenchymal Stem Cells-Derived Extracellular Vesicles Loaded with Doxorubicin for Targeted Inhibition of Hepatocellular Carcinoma

Chunyan Yang; Zixuan Guan; Xincheng Pang; Zengqi Tan; Xiaomin Yang; Xiang Li; Feng Guan

doi:10.3390/cells11172642

Desialylated Mesenchymal Stem Cells-Derived Extracellular Vesicles Loaded with Doxorubicin for Targeted Inhibition of Hepatocellular Carcinoma

Cells. 2022 Aug 25;11(17):2642. doi: 10.3390/cells11172642.

Authors

Chunyan Yang¹, Zixuan Guan¹, Xincheng Pang¹, Zengqi Tan², Xiaomin Yang^{3

4}, Xiang Li², Feng Guan¹

Affiliations

¹ 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.
² Institute of Hematology, School of Medicine, Northwest University, Xi'an 710069, China.
³ Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710069, China.
⁴ Department of Breast Surgery, Tumor Hospital of Shaanxi Province, Xi'an 710069, China.

Abstract

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.

Keywords: ASGPR; desialylation; drug delivery; extracellular vesicles; liver targeting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / metabolism
Doxorubicin / pharmacology
Doxorubicin / therapeutic use
Extracellular Vesicles* / metabolism
Hep G2 Cells
Humans
Liver Neoplasms* / drug therapy
Liver Neoplasms* / metabolism
Mesenchymal Stem Cells* / metabolism

Substances

Doxorubicin

Grants and funding

This study was supported by the National Science Foundation of China (Nos. 82000130, 32071274, 31971211); the Natural Science Foundation of Shaanxi Province (2021SF-294, 2020JM-678); the Science Foundation for Distinguished Young Scholars of Shaanxi Province (2021JC-39); and the Youth Innovation Team of Shaanxi Universities.