Work

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

Year: 2025

Type: article

Abstract: 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.

Source: Aggregate

DOI: 10.1002/agt2.70159