Abstract

Exosomes are nano-sized membranous vesicles produced by nearly all types of cells. Since exosome-like vesicles are produced in an evolutionarily conserved manner for information and function transfer from the originating cells to recipient cells, an increasing number of studies have focused on their application as therapeutic agents, drug delivery vehicles, and diagnostic targets. Analysis of the in vivo distribution of exosomes is a prerequisite for the development of exosome-based therapeutics and drug delivery vehicles with accurate prediction of therapeutic dose and potential side effects. Various attempts to evaluate the biodistribution of exosomes obtained from different sources have been reported. In this review, we examined the current trends and the advantages and disadvantages of the methods used to determine the biodistribution of exosomes by molecular imaging. We also reviewed 29 publications to compare the methods employed to isolate, analyze, and label exosomes as well as to determine the biodistribution of labeled exosomes.

Highlights

  • According to studies conducted over the last half century, most cells on earth produce exosomes or exosome-like particles consisting of a lipid bilayer membrane [1]

  • It is expected that uneven distribution of transporter proteins on the exosome membrane may cause uneven loading of probes when a transporter protein is utilized for the encapsulation of probes

  • Additional transporters are expected to be available for the specific encapsulation of probes in exosomes obtained from different sources with the advancement of research

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Summary

Introduction

According to studies conducted over the last half century, most cells on earth produce exosomes or exosome-like particles consisting of a lipid bilayer membrane [1]. Exosomes, ranging 100–200 nm, from stem cells were reported to mediate the paracrine therapeutic effects of stem cells [6]. Exosomes are important mediators of signal transfer in both multicellular and unicellular organisms. Exosomes derived from MSCs have therapeutic effects on various. The size of exosomes enables their safe systemic administration through multiple routes without the risk of embolism compared to cell-based therapy [42]. A couple of studies have reported that exosomes from MSCs and HEK 293T did not cause toxicity in vivo or in vitro [44–48]. Nano-sized exosomes may reach and accumulate in additional tissues beyond the tissues of therapeutic interest through systemic administration. Analysis of the biodistribution following administration through the intended route is a prerequisite for the development of exosome-based therapeutics

Technologies for Isolation of Exosomes
Quality Control of Exosomes
Bioimaging Modalities
Covalent Binding
Surface Modification
Membrane Integration
Encapsulation
Metabolic Labeling
Analysis of Biodistribution of Exosomes in Literature
Labeling Methods
Imaging Method
Labeling Method Membrane integration
Exosome Isolation Methods
Accumulation of MSC-Exosomes in Damaged Tissues
Tissue Targeting by Exosome Engineering
Findings
Conclusions
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