Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality.

As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosomes offer great potential as a natural therapeutic drug delivery vehicle. The inflammatory responses in various disease models can be attenuated through introduction of super-repressor I kappa B (srI kappa B), which is the dominant active form of I kappa B alpha and can inhibit translocation of nuclear factor kappa B into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srI kappa B into exosomes. We showed that intraperitoneal injection of purified srI kappa B-loaded exosomes (Exo-srI kappa Bs) attenuates mortality and systemic inflammation in septic mouse models. In a biodistribution study, Exo-srI kappa Bs were observed mainly in the neutrophils, and in monocytes to a lesser extent, in the spleens and livers of mice. Moreover, we found that Exo-srlicB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.