Nano-Backpack Engineered Probiotics with Reactive Oxygen Species-Responsive Tungsten Release for Synergistic Therapy...

Integrating probiotics with functional nanomaterials to disrupt the cycle of gut microbiota dysbiosis and reactive oxygen species (ROS) overload is an emerging therapeutic strategy for inflammatory bowel disease (IBD). However, simplistic combinations of therapeutics often result in spatiotemporal mismatch within the gastrointestinal tract, preventing precise intervention at target inflammatory sites. To address this, a composite probiotic system, BSCS@WO₃@PDA is developed, centered around programmed ROS-mediated cascade regulation for intelligent synergistic therapeutic intervention. The system is constructed by electrostatic assembly of polydopamine (PDA)-coated tungsten trioxide nanoparticles onto chitosan-encapsulated Bacillus subtilis (BS), thereby significantly enhancing gastrointestinal stability and promoting prolonged retention in the inflamed colon. At the inflammatory site, the ROS-responsive PDA shell enabled on-demand ROS scavenging while undergoing degradation, leading to the sustained release of tungsten ions. These ions specifically inhibited molybdenum cofactor-dependent nitrate reductase activity in Enterobacteriaceae metabolism, thereby creating a favorable ecological niche for probiotics. Consequently, the retained BS promoted beneficial microbes and metabolites, reversing colitis-associated metabolic disorders and synergistically enhancing intestinal barrier repair. This study proposes a novel paradigm of precise cascade metabolic regulation by integrating ROS scavenging and pathogen inhibition. The BSCS@WO₃@PDA system offers a powerful new strategy for restoring gut microecological homeostasis and treating inflammatory diseases.