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Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake
Name
20013078.2020.1713527.pdf
Description
Published version
Size
757.98 KB
Format
Adobe PDF
Checksum (MD5)
b1b1398ed4bc38932881554515cac6bd
Author(s)
Nishida-Aoki, N
Tominaga, N
Kosaka, N
Ochiya, T
Date Issued
January 1, 2020
Journal
Journal of Extracellular Vesicles
Publisher
Wiley
Citation
Nishida-Aoki, N, Tominaga, N, Kosaka, N and Ochiya, T. 2020. "Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake." Journal of Extracellular Vesicles, 9 (1).
Version
Final published version
Abstract
Extracellular vesicles (EVs) from cancer are delivered both proximal and distal organs. EVs are highly glycosylated at the surface where EVs interact with cells and therefore has an impact on their properties and biological functions. Aberrant glycosylation in cancer is associated with cancer progression and metastasis. However, the biological function of glycosylation on the surface of EV is uncovered. We first demonstrated differential glycosylation profiles of EVs and their originated cells, and distinct glycosylation profiles in a brain-metastatic subline BMD2a from its parental human breast cancer cell line, MDA-MB-231-luc-D3H2LN by lectin blot. We then investigated the roles of surface glycoconjugates on EV uptake. N- and/or O-glycosylation removal of fluorescent-labelled BMD2a EVs enhanced cellular uptake to endothelial cells, suggesting that surface glycosylation has inhibitory effects on cellular uptake. Biodistribution of glycosylation-deprived BMD2a EVs administrated intravenously into mice was further analysed ex vivo using near-infrared lipophilic dye. EVs treated with O-deglycosylation enzymes enhanced the accumulation of EVs to the lungs after 24 h from the injection, while N-deglycosylation did not markedly alter biodistribution. As the lungs are first organs in which intravenous blood flows, we suggest that surface glycosylation of cancer-derived EVs avoid promiscuous adhesion to proximal tissues to be delivered to distant organs.
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Creative Commons Attribution NonCommercial License 4.0
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DOI of Published Version
10.1080/20013078.2020.1713527
