Oxygen vacancy-rich nanosystems eradicate stubborn periodontal biofilms by synergistic EPS degradation, metabolic activation and microbiome restoration.

Abstract

Periodontitis-associated biofilms pose a severe public health threat due to a dual defense mechanism. This involves a protective physical matrix barrier and biological interference from persistent bacteria and microbial dysbiosis. Current strategies often fail to penetrate deeply, eradicate dormant persisters and resolve microbial dysbiosis, leading to biofilm resistance and disease recurrence. In this study, we develop a multifunctional nanoplatform combining photothermal, photodynamic therapy and peroxidase-like catalysis to execute a sequential strategy. This system integrates molybdenum oxide nanodots rich in oxygen vacancy (MoO_3-x) with the photosensitizer indocyanine green (ICG). It exhibits improved optical and enzymatic performance due to the introduced oxygen vacancies. Upon irradiation, the system produces localized hyperthermia and ROS storms to destabilize the biofilm matrix and promote ultrasmall nanodots penetration. The thermal and oxidative stress increase membrane permeability and reactivate metabolism of dormant persisters. Metagenomic analyses confirms that MoO_3-x/ICG-treated biofilms show decreased abundance of key persistence-related genes and great enrichment in metabolic pathways. Additionally, the platform exhibits therapeutic effects and a successful shift towards a healthier oral microbiota in periodontitis model. Overall, MoO_3-x/ICG demonstrates excellent biofilm eradication and successfully prevents biofilm regrowth or secondary infection. This work targets the entire biofilm lifecycle and presents a nanoplatform for long-term management of periodontal infections.