Metal–Organic‐Framework‐Based Hydrogen‐Release Platform for Multieffective Helicobacter Pylori Targeting Therapy and Intestinal Flora Protective Capabilities

Abstract Helicobacter pylori ( H. pylori ) infection is the leading cause of chronic gastritis, peptic ulcer, and gastric cancer. Antibiotics, as traditional method for eliminating H. pylori , have no targeting effect, which causes serious bacterial resistance and gut dysbacteriosis. Moreover, antibiotics can hardly address hyperactive inflammatory response or damaged gastric mucosal barrier caused by H. pylori infection. Here, a pH‐responsive metal–organic framework hydrogen‐generation nanoparticle (Pd(H) @ ZIF‐8) is reported, which is encapsulated with ascorbate palmitate (AP) hydrogel. Both in vitro and in vivo experiments demonstrate that the outer AP hydrogel can target and adhere to the inflammatory site through electrostatic interactions, and is then hydrolyzed by matrix metalloproteinase (MMP) enriching in inflammatory sites. The released Pd(H) @ ZIF‐8 nanoparticles are further decomposed by gastric acid to generate zinc ions (Zn 2+ ) and hydrogen, thus effectively killing H. pylori , alleviating inflammation and restoring impaired gastric mucosa simultaneously. Unexpectedly, this metal–organic framework hydrogen‐generation platform (Pd(H) @ ZIF‐8 @ AP) also has an effect toward avoiding the imbalance of intestinal flora, which thus provides a more precise, effective, and healthy strategy for the treatment of H. pylori infection.