Biodistribution and Delivery Efficiency of Unmodified Tumor-Derived Exosomes
By Tyson J Smyth, M. Kullberg, N. Malik, P. Smith-Jones, M. Graner, T. Anchordoquy. Journal of Controlled Release, 2014
659 citations recorded by the source corpus.
The use of exosomes as a drug delivery vehicle has gained considerable interest. To establish if exosomes could be utilized effectively for drug delivery, a better understanding of their in vivo fate must be established. Through comparisons to liposomal formulations, which have been studied extensively for the last thirty years, we were able to make some comprehensive conclusions about the fate of unmodified tumor-derived exosomes in vivo. We observed a comparable rapid clearance and minimal tumor accumulation of intravenously-injected exosomes, PC:Chol liposomes, and liposomes formulated with the lipid extract of exosomes, suggesting the unique protein and lipid composition of exosomes does not appreciably impact exosomes’ rate of clearance and biodistribution. This rapid clearance along with minimal tumor accumulation of unmodified exosomes limits their use as an anti-cancer drug delivery vehicle; however, when delivered intratumorally, exosomes remained associated with tumor tissue to a significantly greater extent than PC:Chol liposomes. Furthermore, experiments utilizing mice with impaired adaptive or innate immune systems, revealed the significance of the innate immune system along with the complement protein C5 on exosomes’ rate of clearance.
Subfields: Molecular Biology, Renewable Energy, Sustainability and the Environment
View Paper: https://www.semanticscholar.org/paper/7f99857ae410872bd3f1b7f87bf9586beeed5ee5
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Citations in the corpus
- Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey (2016, positive): “Moreover, it has been reported that aggregation may affect the biodistribution of EVs in vivo (12,13).”
- Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting (2015, methodology): “Assessing DiR as an EV labelling tool for biodistribution studies In order to assess the distribution of EVs systemically delivered in mice, the near-infrared (NIR) dye DiR used in earlier studies (24,25) was used for general EV labelling.”
- Exosome Theranostics: Biology and Translational Medicine (2018, background): “Another study has suggested that the clearance of exosomes in vivo is likely controlled by the innate immune system and assisted by the opsonization effects of complement proteins [195].”