Triple-synergistic nanotherapeutics for acute and chronic colitis management via programmable multidimensional modulation

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease characterized by persistent oxidative stress, dysregulated immunity, epithelial barrier disruption, and microbial imbalance, all of which synergistically exacerbate mucosal injury. Addressing these multifactorial challenges remains a critical obstacle in UC therapy. Here, we present a targeted ternary nano-therapeutic platform that integrates cobalt single-atom nanozymes (Co SA), ginsenoside Rb1 (Rb1), and Bifidobacterium bifidum (BB) for multidimensional intervention. Co SA exhibits enzyme-like catalytic activity to scavenge reactive oxygen species and mitigate oxidative stress. Rb1 suppresses pro-inflammatory signaling, promotes tight junction expression, and restores barrier integrity. Meanwhile, BB colonizes the inflamed colon, modulates gut microbiota, and enhances metabolic recovery. Through this synergistic design, the ternary system effectively attenuates oxidative injury, alleviates inflammation, repairs barrier dysfunction, and rebalances the gut microenvironment. In both acute and chronic UC models, this strategy achieved markedly superior therapeutic outcomes compared to individual components or clinical positive controls. Collectively, this work demonstrates a cost-effective, multifunctional, and translatable therapeutic approach, offering a new paradigm for the clinical management of UC.