NIR-activated nanodisguisers for targeted bactericidal action and enhanced electron transfer in periodontitis treatment

Antibacterial treatment for periodontitis faces significant challenges due to the lack of selective bactericidal therapies. In this study, we developed multifunctional nanospheres encapsulated with Fusobacterium nucleatum-derived outer membrane vesicles (OMVs) to target periodontal pathogens specifically. These OMVs act as a "camouflage," allowing the nanospheres to infiltrate bacterial environments undetected, adhere to pathogen surfaces, and maximize therapeutic effects. Direct contact between nanospheres and bacteria accelerates electron transfer, and nanospheres trigger a proliferation of endogenous reactive oxygen species (ROS), leading to oxidative stress and bacterial death. Transcriptomic analysis confirmed that the nanospheres accelerated electron transfer activity and disrupted deoxyribonucleic acid (DNA) repair mechanisms and thiamine metabolism while enhancing bacterial respiration. Though supported by dual photodynamic and photothermal therapies under near-infrared light, the primary mechanism of action focuses on electron transfer and metabolic disruption. In vitro and in vivo experiments demonstrated the nanospheres’ potent biofilm eradication and periodontitis treatment efficacy, offering a promising new approach for selective bacterial targeting. This strategy targets pathogens effectively and preserves the beneficial microbiota, providing an innovative solution for treating periodontitis and other biofilm-related infections.