ectosomes, microvesicles, oncosomes and so on. As a future work, the isolation of
subpopulation of EVs should be warranted to investigate their physiological
characteristics and implications. Furthermore, standardized definition of EVs and
their spectrum is required.
8.2.4 Biological Factors
Given the tropism of EVs, cell-type specific biodistribution can be an important
factor for the possible application of EVs for therapeutic purposes. In spite of the
expectation of tropism effects according to cell types, a direct comparison between
EVs originated from different cell sources (muscle, melanoma and immature bone
marrow) showed similar accumulation in the liver and spleen regardless of the
sources [35]. However, the differential pattern of accumulation was also observed.
Muscle-derived EVs showed higher accumulation in the liver than the others and
immature bone marrow-derived EVs showed higher accumulation in the spleen.
Melanoma-derived EVs were accumulated more in the gastrointestinal tract and the
lungs. This differential accumulation in the liver, lungs and spleen, was not
explained by the size of EVs as the size of EVs originated from different cell types
were similar. Though the size was a critical factor determining in vivo distribution
as aforementioned, different composition of EVs associated with cell sources was
another factor affecting biodistribution. This idea was also supported by the studies
that the tailored EVs having modified molecular composition showed different
biodistribution [51–53]. Composition change of exosomal-tetraspanin complex
affected capability of EVs in their in vivo targeting and showed more accumulation
in the pancreas [51]. Ohno et al. synthesized EVs to target epidermal growth factor
receptor positive breast cancer and showed the tumor accumulation while the most
of the EVs accumulated in liver and spleen [12]. These findings suggested that the
accumulation sites of EVs was mainly mononuclear phagocyte system (or reticuloendothelial system; RES) including liver and spleen, however, the degree of
accumulation and target tissue accumulation could be influenced by molecular
composition of EVs. Contrary to the results of the effect of molecular composition
on in vivo biodistribution, some reports showed that the EVs’ composition effect
was negligible compared with the EVs’ size effect. Intravenously injected EVs were
rapidly cleared and showed minimal tumor accumulation like liposomes and
liposomes generated by exosome compounds [14]. Despite this rapid clearance, the
authors found that intratumorally delivered EVs remained longer than liposomes
which could partly support the potential use of EVs as drug carrier and therapeutics.
The underlying mechanism of differential accumulation patterns of EVs compared with liposomes or micelles remains unknown. Although many studies suggested that molecular composition and tailored EVs could have differential
distribution patterns and enhanced target tissue accumulation, how these molecules
change the physiologic property of EVs has not yet been studied. More importantly,
recent study revealed that EVs isolated from a single cell source have variable
8 Endogenous Radionanomedicine: Biodistribution and Imaging
161
subpopulation of EVs should be warranted to investigate their physiological
characteristics and implications. Furthermore, standardized definition of EVs and
their spectrum is required.
8.2.4 Biological Factors
Given the tropism of EVs, cell-type specific biodistribution can be an important
factor for the possible application of EVs for therapeutic purposes. In spite of the
expectation of tropism effects according to cell types, a direct comparison between
EVs originated from different cell sources (muscle, melanoma and immature bone
marrow) showed similar accumulation in the liver and spleen regardless of the
sources [35]. However, the differential pattern of accumulation was also observed.
Muscle-derived EVs showed higher accumulation in the liver than the others and
immature bone marrow-derived EVs showed higher accumulation in the spleen.
Melanoma-derived EVs were accumulated more in the gastrointestinal tract and the
lungs. This differential accumulation in the liver, lungs and spleen, was not
explained by the size of EVs as the size of EVs originated from different cell types
were similar. Though the size was a critical factor determining in vivo distribution
as aforementioned, different composition of EVs associated with cell sources was
another factor affecting biodistribution. This idea was also supported by the studies
that the tailored EVs having modified molecular composition showed different
biodistribution [51–53]. Composition change of exosomal-tetraspanin complex
affected capability of EVs in their in vivo targeting and showed more accumulation
in the pancreas [51]. Ohno et al. synthesized EVs to target epidermal growth factor
receptor positive breast cancer and showed the tumor accumulation while the most
of the EVs accumulated in liver and spleen [12]. These findings suggested that the
accumulation sites of EVs was mainly mononuclear phagocyte system (or reticuloendothelial system; RES) including liver and spleen, however, the degree of
accumulation and target tissue accumulation could be influenced by molecular
composition of EVs. Contrary to the results of the effect of molecular composition
on in vivo biodistribution, some reports showed that the EVs’ composition effect
was negligible compared with the EVs’ size effect. Intravenously injected EVs were
rapidly cleared and showed minimal tumor accumulation like liposomes and
liposomes generated by exosome compounds [14]. Despite this rapid clearance, the
authors found that intratumorally delivered EVs remained longer than liposomes
which could partly support the potential use of EVs as drug carrier and therapeutics.
The underlying mechanism of differential accumulation patterns of EVs compared with liposomes or micelles remains unknown. Although many studies suggested that molecular composition and tailored EVs could have differential
distribution patterns and enhanced target tissue accumulation, how these molecules
change the physiologic property of EVs has not yet been studied. More importantly,
recent study revealed that EVs isolated from a single cell source have variable
8 Endogenous Radionanomedicine: Biodistribution and Imaging
161