Dual-Targeted Graphitic Cascade Nanozymes for Recognition and Treatment of Helicobacter pylori

Helicobacter pylori (H. pylori) is the major etiological factor of a variety of gastric diseases. However, the treatment of H. pylori is challenged by the destruction of targeted drugs by gastric acid and pepsin. Herein, a dual-targeted cascade catalytic nanozyme PtCo@Graphene@Hemin-2(L-arginine) (PtCo@G@H2A) is designed for the treatment of H. pylori. The dual-targeting ability of PtCo@G@H2A is derived from directly targeting the receptor protein of H. pylori through hemin and responding to the acidic environment to cause charge reversal (protonation of L-arginine) to capture H. pylori, achieving efficient targeting effect. Compared with the single-targeting strategy relying on hemin, the dual-targeting strategy can greatly improve the targeting rate, achieving an increase of 850% targeting rate. At the concentration of NaHCO₃ in intestinal fluid, the surface potential of PtCo@G@H2A can be quickly restored to avoid side effects. Meanwhile, PtCo@G@H2A has pH-responsive oxidase-like activity, which can generate nitric oxide (NO) through a cascade catalytic process that first generates reactive oxygen species (ROS) with oxygen, and further oxidizes L-arginine through ROS, realizing a superior acid-selective bactericidal effect. Overall, it proposes a promising strategy for the treatment of H. pylori that maintains high targeting and therapeutic effects in the environment of gastric acid and pepsin.