Background: Exosomes are cell-derived nanovesicles that play vital roles in intercellular
communication. Recently, exosomes are recognized as promising drug delivery vehicles. Up till now,
how the in vivo distribution of exosomes is affected by different administration routes has not been fully
Methods: In the present study, in vivo distribution of exosomes following intravenous and intraperitoneal
injection approaches was systemically analyzed by tracking the fluorescence-labeled exosomes and
qPCR analysis of C. elegans specific miRNA abundance delivered by exosomes in different organs.
Results: The results showed that exosomes administered through tail vein were mostly taken up by the
liver, spleen and lungs while exosomes injected intraperitoneally were more dispersedly distributed.
Besides the liver, spleen, and lungs, intraperitoneal injection effectively delivered exosomes into the
visceral adipose tissue, making it a promising strategy for obesity therapy. Moreover, the results from
fluorescence tracking and qPCR were slightly different, which could be explained by systemic errors.
Conclusion: Together, our study reveals that different administration routes cause a significant differential
in vivo distribution of exosomes, suggesting that optimization of the delivery route is prerequisite
to obtain rational delivery efficiency in detailed organs.