Bioorthogonal aggregation-induced emission nanoprobes for targeted photodynamic eradication of Gram-negative pathogens in periodontitis.

Periodontitis is a bacteria-driven immune-inflammatory disease associated with progressive periodontal tissue destruction and alveolar bone loss. Conventional treatments rely heavily on broad-spectrum antibiotics, which can promote antimicrobial resistance and disrupt the oral microbiota. Herein, we report a bioorthogonal aggregation-induced emission (AIE)-based nanoprobe, AIE@PEG-DBCO, designed for the selective imaging and photodynamic elimination of Gram-negative periodontal pathogens. By exploiting the metabolic incorporation of 8-azido-3,8-dideoxy-D-manno-octulosonic acid (KDO-N3) into the lipopolysaccharide of Gram-negative bacteria, AIE@PEG-DBCO enables strain-selective fluorescence turn-on and efficient reactive oxygen species generation upon light irradiation. Using Porphyromonas gingivalis as a representative pathogen, the nanoprobe demonstrated effective antibacterial activity and significantly alleviated experimental periodontitis in a rat model. Compared with conventional antibiotic-based therapies, this strategy reduces the risk of drug resistance and minimizes nonspecific disturbance to the oral microbiota by precisely targeting Gram-negative bacteria. This work highlights a materials-based, non-antibiotic approach for periodontal therapy with improved precision and microecological compatibility.