Biomodified Extracellular Vesicles Remodel the Intestinal Microenvironment to Overcome Radiation Enteritis

Ionizingradiation (IR) is associated with the occurrence of enteritis,and protecting the whole intestine from radiation-induced gut injuryremains an unmet clinical need. Circulating extracellular vesicles(EVs) are proven to be vital factors in the establishment of tissueand cell microenvironments. In this study, we aimed to investigatea radioprotective strategy mediated by small EVs (exosomes) in thecontext of irradiation-induced intestinal injury. We found that exosomesderived from donor mice exposed to total body irradiation (TBI) couldprotect recipient mice against TBI-induced lethality and alleviateradiation-induced gastrointestinal (GI) tract toxicity. To enhancethe protective effect of EVs, profilings of mouse and human exosomalmicroRNAs (miRNAs) were performed to identify the functional moleculein exosomes. We found that miRNA-142-5p was highly expressed in exosomesfrom both donor mice exposed to TBI and patients after radiotherapy(RT). Moreover, miR-142 protected intestinal epithelial cells fromirradiation-induced apoptosis and death and mediated EV protectionagainst radiation enteritis by ameliorating the intestinal microenvironment.Then, biomodification of EVs was accomplished via enhancing miR-142expression and intestinal specificity of exosomes, and thus improvedEV-mediated protection from radiation enteritis. Our findings providean effective approach for protecting against GI syndrome in peopleexposed to irradiation.

Automated summary

This study found that exosomes derived from mice exposed to total body irradiation can protect recipient mice against radiation-induced gut injury. MiR-142, highly expressed in exosomes, plays a key role in mediating the protective effect against radiation enteritis by improving the intestinal microenvironment. Biomodification of exosomes through enhancing miR-142 expression and intestinal specificity can further improve the protection against radiation enteritis.