Facile metabolic glycan labeling strategy for exosome tracking

• Published in: Biochimica et biophysica acta Vol. 1862; no. 5; pp. 1091 - 1100
• Main Authors: Lee, Tae Sup, Kim, Young, Zhang, Weiqi, Song, In Ho, Tung, Ching-Hsuan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018
• Subjects: Animals; Cancer; Click chemistry; Click Chemistry - methods; Distribution; Exosome; Exosomes - chemistry; Exosomes - metabolism; Fluorescent Dyes - chemistry; Hexosamines - chemistry; Humans; MCF-7 Cells; Metabolic glycan labeling; Mice; NIH 3T3 Cells; Polysaccharides - chemistry; Polysaccharides - metabolism; Staining and Labeling - methods; Click chemistry; Metabolic glycan labeling; Exosome; Distribution; Cancer
• ISSN: 0304-4165; 0006-3002; 1872-8006; 1878-2434
• DOI: 10.1016/j.bbagen.2018.02.001

Exosomes are nano-sized vesicles derived from the fusion of multivesicular bodies with the surrounding plasma membrane. Exosomes have various diagnostic and therapeutic potentials in cancer and other diseases, thus tracking exosomes is an important issue. Here, we report a facile exosome labeling strategy using a natural metabolic incorporation of an azido-sugar into the glycan, and a strain-promoted azide-alkyne click reaction. In culture, tetra-acetylated N-azidoacetyl-D-mannosamine (Ac4ManNAz) was spontaneously incorporated into glycans within the cells and later redistributed onto their exosomes. These azido-containing exosomes were then labeled with azadibenzylcyclooctyne (ADIBO)-fluorescent dyes by a bioorthogonal click reaction. Cellular uptake and the in vivo tracking of fluorescent labeled exosomes were evaluated in various cells and tumor bearing mice. Highly metastatic cancer-derived exosomes showed an increased self-homing in vitro and selective organ distribution in vivo. Our metabolic exosome labeling strategy could be a promising tool in studying the biology and distribution of exosomes, and optimizing exosome based therapeutic approaches. A facile and effective exosome labeling strategy was introduced by presenting azido moiety on the surface of exosome through metabolic glycan synthesis, and then conjugating a strain-promoted fluorescent dye. [Display omitted] •A facile and effective exosome labeling strategy•Long lasting exosome label•A promising tool for exosome tracking study