9.1 Introduction
Exosomes are a kind of extracellular cell-derived vesicles which have a size in a
range of 30–100 lm and contain various molecules of miRNAs, mRNAs, and
proteins in their spherical structure. Lots of things about characteristics of exosomes
have been unveiled and it is established that exosomes regard to cell-to-cell communication via delivery of their contents to the recipient cells. There are many
reports that diseases are related to specific types of exosomes which can be used as
diagnostic markers. Additionally, the interest in the therapeutic potential of exosomes continues to rise, and the evidence has been accumulated over the last few
years.
There are three important features of exosomes for therapeutic opportunities
(Fig. 9.1) [1]. First one is exosome-mediated disease pathogenesis which implies
the possibility of using exosomes as therapeutic target. Several strategies including
inhibition of exosome-biogenesis, release, cell uptake and targeting of specific
extracellular vesicle components are potentially applicable to block exosomemediated pathogenesis. Next one is exosomes themselves having inherent therapeutic potential such as their involvement of antigen presentation, immune modulation, and tissue repair. Another feature of exosomes for therapeutic potential is
their capability to be used as drug cargo. The spherical feature endogenously
encapsulated by lipid bilayer with various surface proteins enables exosomes to
contain drugs within them and consequent action for specific delivery of the
materials within them. The therapeutic potentials of exosomes have been established in various areas like regenerative medicine, tumor, infection, and organ
transplantation [2].
Imaging and tracking of exosomes are important to understand biodistribution of
exosomes and successful targeted delivery to specific tissue, non-invasively.
Different imaging strategies using fluorescence imaging, bioluminescence reporter
system, magnetic resonance imaging (MRI), and radionuclide imaging have been
applied for tracking of exosomes in vivo [3]. Optical imaging using direct lipophilic
fluorescence dye labeling provides simple methods to observe cell-to-cell communications via exosome transferring [4–7]. Reporter imaging scheme using
fluorescence or bioluminescence provides more specific imaging to exosomes
compared to direct fluorescence dye labeling. Bioluminescence imaging is free
from any false positive signals from retained or freely circulating fluorescent dye
after exosome degradation. However, reporter imaging needs genetic engineering
and has relatively inconsistent signal intensity which depends on the expression of
reporter proteins. Furthermore, optical imaging systems using fluorescence or
bioluminescence has inherent shortcomings of attenuation of signals due to shallow
depth of photon penetration and low availability in clinical field.
Superparamagnetic iron oxide nanoparticles-laden exosomes can be used for MRI
for exosome-tracking [8, 9]. However, this approach needs large amounts of exosomes because of the relatively lower sensitivity of MRI compared with optical
imaging or radionuclide imaging, which further complicates the problem related to
168
S. Ha and D. S. Lee
Exosomes are a kind of extracellular cell-derived vesicles which have a size in a
range of 30–100 lm and contain various molecules of miRNAs, mRNAs, and
proteins in their spherical structure. Lots of things about characteristics of exosomes
have been unveiled and it is established that exosomes regard to cell-to-cell communication via delivery of their contents to the recipient cells. There are many
reports that diseases are related to specific types of exosomes which can be used as
diagnostic markers. Additionally, the interest in the therapeutic potential of exosomes continues to rise, and the evidence has been accumulated over the last few
years.
There are three important features of exosomes for therapeutic opportunities
(Fig. 9.1) [1]. First one is exosome-mediated disease pathogenesis which implies
the possibility of using exosomes as therapeutic target. Several strategies including
inhibition of exosome-biogenesis, release, cell uptake and targeting of specific
extracellular vesicle components are potentially applicable to block exosomemediated pathogenesis. Next one is exosomes themselves having inherent therapeutic potential such as their involvement of antigen presentation, immune modulation, and tissue repair. Another feature of exosomes for therapeutic potential is
their capability to be used as drug cargo. The spherical feature endogenously
encapsulated by lipid bilayer with various surface proteins enables exosomes to
contain drugs within them and consequent action for specific delivery of the
materials within them. The therapeutic potentials of exosomes have been established in various areas like regenerative medicine, tumor, infection, and organ
transplantation [2].
Imaging and tracking of exosomes are important to understand biodistribution of
exosomes and successful targeted delivery to specific tissue, non-invasively.
Different imaging strategies using fluorescence imaging, bioluminescence reporter
system, magnetic resonance imaging (MRI), and radionuclide imaging have been
applied for tracking of exosomes in vivo [3]. Optical imaging using direct lipophilic
fluorescence dye labeling provides simple methods to observe cell-to-cell communications via exosome transferring [4–7]. Reporter imaging scheme using
fluorescence or bioluminescence provides more specific imaging to exosomes
compared to direct fluorescence dye labeling. Bioluminescence imaging is free
from any false positive signals from retained or freely circulating fluorescent dye
after exosome degradation. However, reporter imaging needs genetic engineering
and has relatively inconsistent signal intensity which depends on the expression of
reporter proteins. Furthermore, optical imaging systems using fluorescence or
bioluminescence has inherent shortcomings of attenuation of signals due to shallow
depth of photon penetration and low availability in clinical field.
Superparamagnetic iron oxide nanoparticles-laden exosomes can be used for MRI
for exosome-tracking [8, 9]. However, this approach needs large amounts of exosomes because of the relatively lower sensitivity of MRI compared with optical
imaging or radionuclide imaging, which further complicates the problem related to
168
S. Ha and D. S. Lee