Fluorescence Tracking of Small Extracellular Vesicles In Vivo

In this study, we employed organic and inorganic dyes that have fluorescence under visible or near-infrared light region to stain human umbilical cord (Huc) mesenchymal stem cell (MSC)-, HEK293T cell- and HGC cell-derived small extracellular vesicles (sEVs), and then tracked their fluorescence signals in human gastric cancer xenografted murine models. Several biological characteristics were examined and compared when different dye-stained sEVs in the same tumor model or the same dye-stained sEVs between different tumor models were applied, including sEVs circulation in the blood, biodistribution of sEVs in major organs, and time-dependent tumor accumulation of sEVs. The results demonstrated that distinct tumor accumulation features were presented by sEVs if labeled by different fluorescent dyes, while sEVs derived from different cell lines showed homologous blood circulation and tumor accumulation. To conclude, although fluorescence imaging remains a reliable way to trace sEVs, single staining of sEVs membrane should be obviated in future work when examining the biological fate of sEVs.

Automated summary

This study used organic and inorganic dyes to stain small extracellular vesicles (sEVs) derived from different cell lines, and tracked their fluorescence signals in a gastric cancer xenograft murine model. The study compared the behavior of different dye-stained sEVs in terms of circulation, biodistribution, and tumor accumulation. The results showed that different fluorescent dyes led to distinct tumor accumulation patterns, while sEVs from different cell lines exhibited similar circulation and tumor accumulation behavior. This study suggests that single staining of sEVs membrane should be avoided when examining the biological fate of sEVs.