Metal‐Organic Framework Based Mucoadhesive Nanodrugs for Multifunction Helicobacter Pylori Targeted Eradication, Inflammation Regulation and Gut Flora Protection

Abstract The prevalence of drug‐resistant bacteria presents a significant challenge to the antibiotic treatment of Helicobacter pylori ( H. pylori ), while traditional antimicrobial agents often suffer from shortcomings such as poor gastric retention, inadequate alleviation of inflammation, and significant adverse effects on the gut microbiota. Here, a selenized chitosan (CS‐Se) modified bismuth‐based metal‐organic framework (Bi—MOF@CS‐Se) nanodrug is reported that can target mucin through the charge interaction of the outer CS–Se layer to achieve mucosal adhesion and gastric retention. Additionally, the Bi—MOF@CS‐Se can respond to gastric acid and pepsin degradation, and the exposed Bi—MOF exhibits excellent antibacterial properties against standard H. pylori as well as clinical antibiotic‐resistant strains. Remarkably, the Bi—MOF@CS‐Se effectively alleviates inflammation and excessive oxidative stress by regulating the expression of inflammatory factors and the production of reactive oxygen species (ROS), thereby exerting therapeutic effects against H. pylori infection. Importantly, this Bi—MOF@CS‐Se nanodrug does not affect the homeostasis of gut microbiota, providing a promising strategy for efficient and safe treatment of H. pylori infection.