In vivo activation of pH-responsive oxidase-like graphitic-nanozymes for selective killing of Helicobacter pylori

Abstract Helicobacter pylori infection is a major etiological factor in various gastric diseases. However, clinical antibiotic triple therapy for H. pylori often encounters such critical problems as continuously decreased therapeutic efficacy and symbiotic bacteria experiencing severe side effects. Herein, we developed an in vivo activatable pH-responsive graphitic nanozyme, PtCo@Graphene (PtCo@G), for the selective treatment of H. pylori infections. Such nanozymes can resist gastric acid corrosion and activate oxidase-like activity to stably generate reactive oxygen species only in the acidic gastric milieu which endows them with superior selective bactericidal property. C18-PEGn-Benzeneboronic acid molecules were further modified on the PtCo@G, improving its targeting capability to H. pylori. Under acidic gastric pH, graphitic nanozymes showed notable bactericidal activity toward H. pylori, while no bacterial killing was observed under the intestinal condition. In the H. pylori-infected mouse model, high antibacterial capability toward H. pylori and negligible side effects toward normal tissues and symbiotic bacteria were also achieved. This graphitic nanozyme performs the desired enzyme-like activity at corresponding physiological sites and may address critical issues in the clinical treatment of H. pylori infections.