Hitchhiking novel nanozymes on Bacillus licheniformis as an interactive reinforced bioactive platform for multifaceted therapy of ulcerative colitis.

Managing ulcerative colitis (UC) remains a great challenge in clinical practice due to the intricate interplay among oxidative stress, inflammatory cascades, gut microbiota dysbiosis, and compromised barrier function. Herein, we propose a novel interactive reinforced bioactive platform, termed BL@APPCs, designed to enable precise, multifaceted, and sustained therapy for UC. Each bioactive unit within this platform consists a single Bacillus licheniformis (BL) integrated with multiple hybrid nanozymes (APPCs). These nanozymes can imitate the intracellular antioxidant defense system via their high density of reactive oxygen species-reacting active sites, including monodisperse ultrafine nanoceria (5 nm) and polyphenolic groups, and enable the loading of additional agents, like flavonoids. With their pH-sensitive and mucoadhesive single-cell nanocoating, BL@APPCs demonstrated enhanced accumulation and retention on inflamed colonic mucosa, enabling the controlled delivery and targeted uptake of the hitchhiked APPCs. These APPCs safeguarded cells and probiotics from oxidative stress while mitigating inflammation by leveraging their cascade enzymatic activities alongside the pharmacological activities of flavonoids. As a result, BL@APPCs demonstrated significant therapeutic efficacy in preventing and treating UC in murine models. The BL@APPC treatment effectively restored intestinal barrier functions and remodeled gut microbial homeostasis. Collectively, harnessing their hierarchical assembly structure, diverse biological activities, hierarchical targeting advantages, and favorable biosafety, BL@APPCs facilitate interactions among advanced nano-catalytic therapy, bacteriotherapy, and flavonoid therapy, thereby establishing an innovative localized and comprehensive strategy for managing UC.