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

() 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 Fe. In acidic stomach conditions, TA-FeHMSN@Amox generates bactericidal OH through Fenton/Fenton-like reactions of the degraded product Fe and hydrogen peroxide (HO) 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 HO. The acidity-responsive CDT combined with reduced antibiotic usage ensures superior therapeutic efficacy and biocompatibility with intestinal flora, providing a highly potent strategy for treating infections in the dynamic stomach environment.