Inflammatory microenvironment-triggered bimetallic nanozymes as ultrasonic-augmented ROS generator for effective killing of Helicobacter pylori

Helicobacter pylori ( H. pylori ) infection, affecting more than half of the world's population, remains the primary etiological driver of stomach cancer. The efficacy of standard antibiotic-based quadruple therapy is declining due to the antibiotic resistance. To address this critical challenge, we developed an inflammation-responsive self-cascading reactive oxygen species (ROS) nanogenerator (BiPt@BSA-PpIX@AP) that synergizes nanozyme catalysis and sonodynamic therapy (SDT) for precision H. pylori eradication. Upon ultrasound activation, the system demonstrated dual-modal ROS amplification. BiPt nanozymes catalytically converted endogenous H 2 O 2 to •OH and O 2 , while protoporphyrin (PpIX) generated more 1 O 2 than free PpIX through enhanced sonoluminescence energy transfer. In H. pylori infected mouse model, the BiPt@BSA-PpIX@AP actively targeted submucosa colonized H. pylori owing to metalloproteinases (MMPs)-triggered hydrolysis and protonation effect, and further eradicated H. pylori and its biofilm by producing ROS. Unlike triple therapy, the nanogenerators had negligible side effects on the normal gut microbiota. This microenvironment-driven self-enhancing ROS nanogenerators have great potential for the treatment of H. pylori infection.