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Extracellular vesicles (EVs) are considered sophisticated vehicles for cell-to-cell communication, thanks to the possibility of handling a variable cargo in a shell with multiple types of decoders. Surface glycosylation of EVs is a method that could be used to control their interaction with different cells and, consequently, the biodistribution of the vesicles in the body. Herein, we produced EVs derived from mouse liver proliferative cells, and we treated them with neuraminidase, an enzyme that digests the terminal sialic acid residues from glycoproteins. Afterwards, we labeled the EVs directly with [124I]Na and injected them in mice intravenously or into the hock. The amount of radioactivity in major organs was measured at different time points after administration both in vivo using positron emission tomography and ex vivo (after animal sacrifice) using dissection and gamma counting. The results showed that intravenous …