Biomodified Extracellular Vesicles Remodel the Intestinal Microenvironment to Overcome Radiation Enteritis

Ionizing
radiation (IR) is associated with the occurrence of enteritis,
and protecting the whole intestine from radiation-induced gut injury
remains an unmet clinical need. Circulating extracellular vesicles
(EVs) are proven to be vital factors in the establishment of tissue
and cell microenvironments. In this study, we aimed to investigate
a radioprotective strategy mediated by small EVs (exosomes) in the
context of irradiation-induced intestinal injury. We found that exosomes
derived from donor mice exposed to total body irradiation (TBI) could
protect recipient mice against TBI-induced lethality and alleviate
radiation-induced gastrointestinal (GI) tract toxicity. To enhance
the protective effect of EVs, profilings of mouse and human exosomal
microRNAs (miRNAs) were performed to identify the functional molecule
in exosomes. We found that miRNA-142-5p was highly expressed in exosomes
from both donor mice exposed to TBI and patients after radiotherapy
(RT). Moreover, miR-142 protected intestinal epithelial cells from
irradiation-induced apoptosis and death and mediated EV protection
against radiation enteritis by ameliorating the intestinal microenvironment.
Then, biomodification of EVs was accomplished via enhancing miR-142
expression and intestinal specificity of exosomes, and thus improved
EV-mediated protection from radiation enteritis. Our findings provide
an effective approach for protecting against GI syndrome in people
exposed to irradiation.