Targeted catalytic eradication of antibiotic-resistant Helicobacter pylori by a pH-activated Fe-doped nanozyme

The increasing prevalence of antibiotic-resistant Helicobacter pylori (R-H. pylori) poses a significant clinical challenge, contributing to persistent gastritis, peptic ulcers, and gastric cancer. Conventional antibiotic therapies are increasingly limited by resistance, incomplete eradication, and disruption of the gut microbiota. To address these challenges, we developed pH-responsive iron-doped ammonium citrate carbon dots (Fe-CDs), a nanozyme with intrinsic specificity for targeting and eradicating R-H. pylori within the acidic gastric microenvironment. Fe-CDs exhibit dual oxidase (OXD)- and peroxidase (POD)-like catalytic activities that are selectively activated under acidic conditions, driving the localized generation of reactive oxygen species (ROS) via Fenton and Fenton-like reactions involving Fe(II) and endogenous hydrogen peroxide (H₂O₂). The nanozyme shows strong binding affinity for H. pylori through ammonium (NH₄⁺)-mediated interactions and specifically targets Urel, thereby inhibiting urease activity and disrupting bacterial acid resistance. This dual mechanism-acid-enhanced ROS production combined with urease suppression-confers potent bactericidal effects against R-H. pylori while preserving commensal microbiota and minimizing off-target damage. Transcriptomic analysis of infected gastric tissue revealed that Fe-CDs induce ROS-mediated stress pathways and metabolic disruption in H. pylori. In vivo studies confirmed that Fe-CDs significantly reduce bacterial load in R-H. pylori-infected mice with negligible toxicity. These findings highlight Fe-CDs as a targeted, antibiotic-free therapeutic strategy for resistant gastric infections and offer a promising alternative to conventional treatments.