pH-responsive self-sacrificing cascade nanozyme platform for selective eradication of Helicobacter pylori

Helicobacter pylori ( H. pylori ) infection poses a significant global health burden and is implicated in various chronic gastric diseases. However, current antibiotic therapies are limited by non-specific bacterial targeting, which often results in antimicrobial resistance and disruption of gut microbial homeostasis. To overcome these limitations, we developed a pH-responsive, self-sacrificing cascade nanozyme platform, ZnO 2 -CuNiS@G-Ch, for the targeted eradication of H. pylori . In the highly acidic gastric environment, ZnO 2 rapidly decomposes to release Zn 2+ and H 2 O 2 , initiating selective bacterial killing. Furthermore, the generated H 2 O 2 triggers the cascade activation of CuNiS@G-Ch nanozyme, exhibiting multiple enzyme-like activities-peroxidase (POD), catalase (CAT), and oxidase (OXD) to locally generate reactive oxygen species (ROS) and O 2 , thereby amplifying the bactericidal effect. Notably, upon transiting to the neutral intestinal milieu, the degradation of ZnO 2 was completely suppressed, effectively halting downstream nanozyme activity and preserving the gut microbiota. Comprehensive in vitro and in vivo studies confirmed the robust anti- H. pylori efficacy of ZnO 2 -CuNiS@G-Ch, alongside potent anti-inflammatory effects, gastric mucosal protection, and excellent biocompatibility. This work provides a selective, efficient, and microbiota-friendly strategy for H. pylori therapy, offering a promising alternative to conventional broad-spectrum antibiotics.