Polydopamine Modified Ceria Nanorods Alleviate Inflammation in Colitis by Scavenging ROS and Regulating Macrophage M2 Polarization

Background: Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy. Methods: CeO 2 @PDA-PEG (CeO 2 @PP) were synthesized by modifying ceria (CeO 2 ) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO 2 @PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO 2 @PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO 2 @PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO 2 @PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model. Results: Physicochemical property results demonstrated that PDA and PEG modification endowed CeO 2 nanorods with excellent dispersibility and colloidal stability. CeO 2 @PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO 2 @PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO 2 @PP have great biocompatibility and biosafety. Animal experiments have shown that CeO 2 @PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury. Conclusion: The nanoplatform CeO 2 @PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy. Graphical Abstract: Keywords: ceria, PDA, nanozyme, antioxidation, anti-inflammation, macrophage polarization, colitis