Antibiotic-Augmented Chemodynamic Therapy for Treatment of Helicobacter pylori Infection in the Dynamic Stomach Environment

Helicobacter pylori (H. pylori) is one of the main causes of peptic ulcer disease and gastric cancer. The overuse of antibiotics leads to bacterial drug resistance and disruption to the gut microbiome. Herein, a nanoparticle (TA-FeHMSN@Amox) was developed, comprising amoxicillin (Amox)-loaded iron-engineered hollow mesoporous silica as the core and a metal–polyphenol shell formed by tannic acid (TA) and Fe3+. In acidic stomach conditions, TA-FeHMSN@Amox generates bactericidal ·OH through Fenton/Fenton-like reactions of the degraded product Fe2+ and hydrogen peroxide (H2O2) at the infection site, achieving chemodynamic therapy (CDT). Moreover, released amoxicillin enhances therapeutic efficacy by impeding the self-repair of the bacterial cell wall damaged by CDT, overcoming the limitations of ineffective CDT under conditions lacking sufficient acidity and H2O2. The acidity-responsive CDT combined with reduced antibiotic usage ensures superior in vivo therapeutic efficacy and biocompatibility with intestinal flora, providing a highly potent strategy for treating H. pylori infections in the dynamic stomach environment.