Cerium Oxide-Loaded Exosomes Derived From Regulatory T Cells Ameliorate Inflammatory Bowel Disease by Scavenging Reactive Oxygen Species and Modulating the Inflammatory Response

Simei Yue,1,* Lingjiao Gong,1,* Yulin Tan,1 Xiaodan Zhang,1 Fei Liao1– 3 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000, People’s Republic of China; 2Wuhan University Shenzhen Research Institute, Shenzhen, Guangdong, 518000, People’s Republic of China; 3Central Laboratory of Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Liao, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430000, People’s Republic of China, Email [email protected]: Abnormal immune homeostasis, which leads to the accumulation of reactive oxygen species (ROS) and an inflammatory response, plays a crucial role in accelerating the progression of inflammatory bowel disease (IBD). The lack of targeted therapeutic strategies significantly hampers the efficacy of clinical treatments for IBD. This study presents cerium oxide nanoparticle-loaded regulatory T cell-derived exosomes (exo@nCeO) as innovative anti-inflammatory and antioxidant agents specifically designed to address the effects of immune dysregulation.Methods: In this work, the morphology and antioxidant properties of nano-cerium oxide were characterized using transmission electron microscopy, as well as hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl radical assays. Tumor necrosis factor-α and dextran sulfate sodium were employed to establish cellular and animal models of IBD. The impact of exo@nCeO on ROS scavenging and anti-inflammatory activity in intestinal epithelial cells was assessed using dihydroethidium and 2,7-dichlorodihydrofluorescein staining, Western blotting, and apoptosis flow cytometry analysis. Hematoxylin and eosin staining, along with immunohistochemistry and immunofluorescence staining, were utilized to evaluate intestinal epithelial inflammation and ROS levels in the IBD mouse model.Results: The findings demonstrate that exo@nCeO possesses augmented anti-inflammatory properties and ROS scavenging abilities in intestinal epithelial cells. In murine models of IBD, exo@nCeO effectively maintained the integrity of the intestinal epithelial barrier and impeded the progression of IBD.Conclusion: This study introduces a novel therapeutic approach for IBD and underscores a potential strategy for addressing diseases associated with inflammation and oxidative stress. Keywords: inflammatory bowel disease, regulatory T cells, exosomes, cerium oxide