Enhancing intracellular ROS scavenging by chondroitin sulfate-modified ceria nanozymes for the treatment of inflammatory bowel disease and enteropathic arthritis.

Oxidative stress is a key factor in the progression of inflammatory bowel disease (IBD) and enteropathic arthritis, and scavenging excessive intracellular reactive oxygen species (ROS) is an effective therapeutic strategy. Chondroitin sulfate-modified cerium oxide nanozymes (CS-CNPs) were synthesized for the first time in this study with dual-cell targeting properties, which regulated the redox homeostasis of the inflammatory sites of the colon and joints through scavenging intracellular ROS, and thus treating IBD and enteropathic arthritis. The results showed that CS-CNPs possessed multiple mimetic antioxidant enzyme activities and could target inflammatory intestinal epithelial cells and macrophages to scavenge ROS. The good cellular targeting of CS-CNPs enhanced the ability to scavenge ROS from inflammatory cells in the colon of colitis mice, and they produced a good IBD therapeutic effect by inhibiting the intestinal inflammatory response and repairing the damaged intestinal mucosal barrier. In addition, for the treatment of experimental enteropathic arthritis, CS-CNPs demonstrated colonic and joint inflammatory site targeting, and exerted anti-inflammatory effects by scavenging ROS. The conveniently synthesized dual-targeted nanozymes lay the foundation for "kill two birds with one stone" in treating IBD and enteropathic arthritis, as well as an effective solution for the multi-targeted treatment of oxidative stress-related diseases.