Antibiotic-Augmented Chemodynamic Therapy for Treatment of <i>Helicobacter pylori</i> Infection in the Dynamic Stomach Environment.

Abstract

<i>Helicobacter pylori</i> (<i>H. pylori</i>) 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 <b>·</b>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 <i>in vivo</i> therapeutic efficacy and biocompatibility with intestinal flora, providing a highly potent strategy for treating <i>H. pylori</i> infections in the dynamic stomach environment.