Biocompatible Nanozyme Shell‐Armed Probiotic with Inflammation Targeting and Scavenging Properties Enables Effective Treatment of Colitis

Abstract Coupling probiotics with lesion targeting and inflammation control properties without complex chemical modifications is crucial for preserving their native bioactivity, but remains challenging. Herein, metformin as a functional self‐modulated alkaline reagent is incorporated to achieve the rapid and biocompatible construction of a polydopamine‐based nanozyme shell (DMCe) on the surface of probiotics, thus avoiding the biological toxicity caused by traditional triggering methods. DMCe can not only serve as a robust physical barrier to protect probiotics from the invasion of digestive juices and antibiotics, but also synergistically scavenge reactive oxygen species (ROS) at colitis lesions via the intrinsic antioxidant property of catechol and the catalase‐mimicking activity of cerium oxide. It is worth noting that during the process of scavenging ROS, the originally harmful ROS can be utilized by DMCe as reactive components to facilitate chemical reactions between the modified probiotics and colitis lesions, thus achieving prolonged inflammation targeting for up to 7 days. In addition, nanozyme shell‐armed probiotics can improve microbial community composition and increase the levels of short‐chain fatty acids. By integrating inflammation targeting, ROS scavenging, and microbiome remodeling, nanozyme shell‐armed probiotics can significantly reduce inflammation levels and promote healing of the mucosal barrier in a mouse colitis model.