Exosome-based Delivery of Super-Repressor IκBα Relieves Sepsis-Associated Organ Damage and Mortality
Other Titles
Exosome-based delivery of super-repressor I kappa B alpha relieves sepsis-associated organ damage and mortality
Authors
Hojun Choi ; Youngeun Kim ; Amin Mirzaaghasi ; Jaenyoung Heo ; Yu Na Kim ; Ju Hye Shin ; Seonghun Kim ; Nam Hee Kim ; Eunae Sandra Cho ; Jong In Yook ; Tae-Hyun Yoo ; Eunjoo Song ; Pilhan Kim ; Eui-Cheol Shin ; Kyungsoo Chung ; Kyungsun Choi ; Chulhee Choi
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 IκB (srIκB), which is the dominant active form of IκBα and can inhibit translocation of nuclear factor κB into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srIκB into exosomes. We showed that intraperitoneal injection of purified srIκB-loaded exosomes (Exo-srIκBs) attenuates mortality and systemic inflammation in septic mouse models. In a biodistribution study, Exo-srIκBs 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-srIκB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.