Protonated Charge Reversal Nanodrugs for Active Targeting Clearance of Helicobacter Pylori Accompanied by Gut Microbiota Protection

Abstract Helicobacter pylori ( H. pylori ) is listed as a definite carcinogen and clinical triple therapy is less satisfactory because H. pylori colonizes beneath the gastric mucous layer and easily forms biofilm. More importantly, the frequent and excessive use of antibiotics causes a disorder of gut microbiota due to the lack of targeting to H. pylori . Here, a kind of protonated charge reversal metal based nanodrugs (MNDs)—ZnO‐Ag‐mercaptoacetamide@chitosan for H. pylori eradication treatment without affecting beneficial gut microbiota is prepared. In H. pylori infected mouse model, the MNDs actively target submucosa colonized H. pylori owing to mucous penetrability and protonation effect, and further eradicate H. pylori and its biofilm by producing metal ions and reactive oxygen species. Transcriptomic analysis shows that there are no obvious side effects to intestinal microorganisms during the treatment. Besides, it is found that the MNDs are great potential to remove gastric inflammation along with the blocking of inflammatory pathways and the reduction of virulence factors, which is related to the infiltration of CD4 + T cells to clear H. pylori .