A triple-responsive nanozyme platform of AgAu–CeO2 heterojunction integrated with probiotics for precision antibacterial therapy in periodontitis

Abstract

Nanozymes hold significant promise for biomedical applications; however, their clinical translation is hindered by the mismatch between physiological conditions and their optimal catalytic environments, particularly with respect to temperature and pH. To address this challenge, we developed a multifunctional composite nanozyme (AgAu C-L, formed by covalent conjugation of AgAu@CeO₂ with Lactobacillus reuteri) by anchoring an ultrasmall cerium dioxide (CeO₂) nanozyme with peroxidase (POD)-like activity onto silver-gold nanocages (AgAu NCs), and integrating it with Lactobacillus reuteri (L. reuteri). Upon near-infrared light irradiation, the localized surface plasmon resonance effect of AgAu NCs induced dual regulatory mechanisms: photothermal heating, which elevated local temperature to enhance catalytic efficiency, and interfacial electron transfer, which promoted Ce³⁺/Ce⁴⁺ redox cycling to sustain catalytic activity. Simultaneously, L. reuteri modulated the local pH through the secretion of lactic and acetic acids, creating a favorable acidic microenvironment for enzyme function. This triple-modulation strategy markedly enhanced the POD-like activity of CeO₂, triggering a robust reactive oxygen species burst that effectively disrupted periodontal biofilms and eliminated pathogenic bacteria. Furthermore, the composite interfered with microbial metabolic pathways, reducing biofilm formation and virulence. Our findings establish a powerful nanozyme-based platform for periodontitis treatment and provide a broadly applicable strategy for optimizing nanozyme performance in vivo.