Combating drug-resistant helicobacter pylori infection with zinc peroxide-based nanoparticles: A ROS reservoir via photochemical reaction

Abstract

Addressing the challenge of treating Helicobacter pylori infection while ensuring the safety of other microorganisms, such as intestinal microbiota, is of paramount importance. In this research, we synthesized a liposome-encapsulated composite of ZnO2 and chlorin e6 (ZnO2-Ce6@lipo) to achieve the acid-responsive release of Zn2+, H2O2, and Ce6 in the stomach, thereby creating a versatile reactive oxygen species (ROS) reservoir for stomach infection therapy. The incorporation of liposomes improves the dispersion and the targeting towards mucosal lesions. Within the gastric environment, ZnO2 displays a more efficient and prolonged acid-neutralization capacity compared to traditional proton pump inhibitors (PPI), while also generating bactericidal Zn2+ and H2O2. Furthermore, abundant H2O2 was photolyzed by 460 nm blue laser irradiation to generate highly active ·OH. The O2 produced by the hydrolysis of H2O2 effectively overcame the O2-dependent limitations associated with Ce6-mediated photodynamic therapy (PDT). Serving as a ROS reservoir, the PDT system demonstrated remarkable bactericidal effectiveness, as evidenced by in vitro and in vivo experiments, achieving > 99.999 % eradication of both standard strain and multidrug-resistant H. pylori strains. Compared to traditional triple therapy, this gastric acid-responsive system minimizes its impact on intestinal microbiota, demonstrating excellent biocompatibility, and introduces a novel ROS reservoir for PDT against H. pylori.