Cascaded Nanozyme Based pH‐Responsive Oxygenation for Targeted Eradication of Resistant Helicobacter Pylori

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2024-09, Vol.20 (36), p.e2401059-n/a
• Main Authors: Tong, Yue, Liu, Qian, Fu, Hongli, Han, Mengfan, Zhu, Hanchen, Yang, Kun, Xu, Le, Meng, Meng, Yin, Yongmei, Xi, Rimo
• Format: Article
• Language: English
• Subjects: Acidic oxides; Antiinfectives and antibacterials; Biocompatibility; Biomedical materials; Cascade chemical reactions; cascade reactions; Catalase; Catalysis; Chitosan; Cobalt; Helicobacter pylori; Hydrogen peroxide; nanozyme; Oxygenation; Peroxidase; Pigments; Prussian blue analog; Staining; Superoxide dismutase
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202401059

Nanozymes, as substitutes for natural enzymes, are constructed as cascade catalysis systems for biomedical applications due to their inherent catalytic properties, high stability, tunable physicochemical properties, and environmental responsiveness. Herein, a multifunctional nanozyme is reported to initiate cascade enzymatic reactions specific in acidic environments for resistant Helicobacter pylori (H. pylori) targeting eradication. The cobalt‐coated Prussian blue analog based FPB‐Co‐Ch NPs displays oxidase‐, superoxide dismutase‐, peroxidase‐, and catalase‐ mimicking activities that trigger •O2−${\mathrm{O}}_2^ - {\bm{\ }}$ and H2O2 to supply O2, thereby killing H. pylori in the stomach. To this end, chitosan is modified on the surface to exert bacterial targeted adhesion and improve the biocompatibility of the composite. In the intestinal environment, the cascade enzymatic activities are significantly inhibited, ensuring the biosafety of the treatment. In vitro, sensitive and resistant strains of H. pylori are cultured and the antibacterial activity is evaluated. In vivo, murine infection models are developed and its success is confirmed by gastric mucosal reculturing, Gram staining, H&E staining, and Giemsa staining. Additionally, the antibacterial capacity, anti‐inflammation, repair effects, and biosafety of FPB‐Co‐Ch NPs are comprehensively investigated. This strategy renders a drug‐free approach that specifically targets and kills H. pylori, restoring the damaged gastric mucosa while relieving inflammation. A four‐in‐one nanozyme is reported with the cascaded SOD‐, CAT‐, POD‐, and OXD‐mimicking activities. Ferrocene is novelly doped in Prussian blue and used as the core and Co3O4 NPs are modified to provide multifunctional hybrid cascaded nanozyme activities. With the encapsulation of chitosan, this nanozyme exhibits excellent therapeutic potential for H. pylori infections in vitro and in vivo.