Fimbriae‐Targeted Peptide‐Selenoviologen Cyclophane Complex for Enhanced Photodynamic Therapy of Periodontitis

ABSTRACT Photodynamic therapy (PDT) holds great promise for treating periodontitis, yet its clinical efficacy is limited by the lack of specificity of conventional photosensitizers toward pathogenic bacteria. Herein, we developed a targeted photosensitizer system using a host–guest supramolecular strategy to address this challenge. The design features a selenoviologen cyclophane ( SeVB ) host molecule that encapsulates a Porphyromonas gingivalis ( P. gingivalis )‐specific binding peptide (PQGPPQF, abbreviated PQ), forming the supramolecular complex SeVB⊃PQ . Leveraging the high affinity of PQ for P. gingivalis fimbriae, SeVB⊃PQ demonstrates exceptional bacterial targeting capability, achieving a colocalization coefficient of 0.669. Upon light activation, SeVB⊃PQ generates elevated intracellular reactive oxygen species while disrupting adenosine triphosphate synthesis in P. gingivalis , resulting in a 33.12% enhancement in antimicrobial activity compared to SeVB alone at 0.1 µM. Beyond its direct bactericidal effects, SeVB⊃PQ ‐mediated PDT effectively restores subgingival microbiome homeostasis and attenuates microbial pathogenicity through metabolic modulation. In comparative studies with both SeVB and clinical‐grade methylene blue (MB), SeVB⊃PQ demonstrated superior performance in mitigating inflammatory tissue damage and promoting periodontal regeneration. This targeted supramolecular platform not only advances PDT for periodontitis treatment but also provides a novel paradigm for the rational design of pathogen‐selective photosensitizers.