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.

中文翻译：

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基于外来体的超级抑制因子IκBα的释放可减轻败血症相关器官的损害和死亡率。

由于细胞外小泡通过将细胞物质转移到受体细胞而在细胞间通讯中发挥积极作用，因此外泌体具有巨大的潜力，可作为天然的治疗药物递送载体。可以通过引入超级阻遏物IκB（srIκB）减轻各种疾病模型中的炎症反应，该蛋白是IκBα的主要活性形式，可以抑制核因子κB向核内移位。我们先前开发的光遗传工程外泌体系统（EXPLOR）用于将大量srIκB加载到外泌体中。我们显示，腹腔内注射纯化的srIκB负载的外泌体（Exo-srIκBs）可以减轻败血症小鼠模型的死亡率和系统性炎症。在一项生物分布研究中，主要在嗜中性粒细胞中观察到Exo-srIκBs，小鼠脾脏和肝脏中的单核细胞含量较低。此外，我们发现Exo-srIκB减轻了单核THP-1细胞和人脐静脉内皮细胞的炎症反应。