Sulfasalazine- and Cerium Ion-Loaded Polymersomes with Enhanced RONS Scavenging and Colonic Mucosal Repair Ameliorate Experimental Colitis

Inflammatory bowel disease (IBD) is a relapsing gastrointestinal disorder depicted by persistent oxidative/nitrosative stress, mucosal barrier disruption, and maladaptive immune activation. Herein, we report that sulfasalazine- and cerium ion-loaded polymersomes (SSZ/Ce-Some) that effectively treat IBD through superior capability of scavenging reactive oxygen and nitrogen species (RONS) and promotion of colonic mucosal repair. SSZ/Ce-Some exhibits potent superoxide dismutase (SOD)-like and catalase (CAT)-like catalytic activities, efficiently scavenges representative ROS, and markedly generates oxygen. Its excellent neutralization of RNS (NO) together with superoxide indicates inhibition of tissue-destructive peroxynitrite. SSZ/Ce-Some inhibits inflammatory macrophages and dendritic cell activation and suppresses pro-inflammatory cytokine secretion. In acute colitis, SSZ/Ce-Some accumulates in inflamed colons, alleviates intestinal inflammation, and preserves epithelial tight junction integrity. Moreover, oral SSZ/Ce-Some in a mucoadhesive hydrogel safely and effectively treats chronic Crohn’s disease, with tissue repair and immune regulation. Overall, SSZ/Ce-Some with superior RONS-detoxifying capacity represents a promising therapeutic strategy for IBD treatment.