Tracking of Extracellular Vesicles' Biodistribution: New Methods and Approaches

Abstract

Extracellular vesicles (EVs) are nanosized lipid bilayer vesicles that are released by almost all cell types. They range in diameter from 30 nm to several micrometres and have the ability to carry biologically active molecules such as proteins, lipids, RNA, and DNA. EVs are natural vectors and play an important role in many physiological and pathological processes. The amount and composition of EVs in human biological fluids serve as biomarkers and are used for diagnosing diseases and monitoring the effectiveness of treatment. EVs are promising for use as therapeutic agents and as natural vectors for drug delivery. However, the successful use of EVs in clinical practice requires an understanding of their biodistribution in an organism. Numerous studies conducted so far on the biodistribution of EVs show that, after intravenous administration, EVs are mostly localized in organs rich in blood vessels and organs associated with the reticuloendothelial system, such as the liver, lungs, spleen, and kidneys. In order to improve resolution, new dyes and labels are being developed and detection methods are being optimized. In this work, we review all available modern methods and approaches used to assess the biodistribution of EVs, as well as discuss their advantages and limitations.

Keywords: biodistribution; bioluminescence; computed tomography; exosomes; extracellular vesicles; fluorescence; magnetic resonance imaging; microvesicles; positron emission tomography; single photon emission computed tomography.

Figure 1

Biodistribution profile of EVs after i.v. injection into the tail vein. (A) Route of EVs’ distribution; through the bloodstream, EVs enter the small circle of the circulation, enter the lungs, then accumulate in the liver and spleen, are detected in the GI tract, and finally are detected in the kidneys and bladder. (B) The frequency of detection of EVs after i.v. administration in organs (based on the reviewed data).