Oral liposomal co-delivery of ultrasmall ceria and 5-aminosalicylic acid alleviates DSS colitis via ROS scavenging and microbiome remodeling

Inflammatory bowel disease (IBD) is a refractory gastrointestinal disorder characterized by sustained intestinal inflammation, mucosal barrier dysfunction, and gut dysbiosis. Excess reactive oxygen species (ROS) is a key driver of these pathological processes. Although CeO₂-based nanozymes can scavenge ROS, its clinical application is limited by poor aqueous stability. Here, we developed an oral nanozyme by co-encapsulating ultrasmall CeO₂ nanoparticles and the clinical drug 5-aminosalicylic acid (5-ASA) within liposomes. The resulting formulation (CeLA) exhibited excellent colloidal stability and robust ROS-scavenging activity, and provided marked cytoprotection against oxidative stress in vitro. In a dextran sulfate sodium (DSS)-induced colitis model, CeLA alleviated clinical symptoms, restored intestinal barrier integrity, and suppressed pro-inflammatory cytokine expression. Notably, CeLA also reshaped the dysbiotic gut microbiome by reducing pro-inflammatory bacterial taxa. This multifunctional nanozyme integrates antioxidant, anti-inflammatory, and microbiome-modulating effects, offering a promising therapeutic strategy for IBD.