A phthalocyanine-peptide conjugate for targeted photodynamic therapy of dental caries with concurrent tooth whitening effect.

Antimicrobial photodynamic therapy (aPDT) has been clinically used in managing periodontal and endodontic infections; however, its application in another bacteria-induced dental condition, dental caries, remains largely unexplored. In this study, we exploited aPDT's therapeutic efficacy in dental caries using a phthalocyanine (Pc)-antimicrobial peptide (AMP) conjugate, Pc-B8. Compared to conventional clinical dental photosensitizers (e.g., porphyrin and methylene blue), Pc exhibits enhanced reactive oxygen species yield and deeper tissue penetration. Conjugation with AMP addresses the limitations of Pc in dental applications by: 1) improving aqueous solubility, 2) increasing electrostatic attraction to bacterial surface, and 3) providing persistent antimicrobial activity beyond the transient aPDT effect. We experimentally validated the antimicrobial efficacy of Pc-B8 against cariogenic bacteria, efficient inhibition of biofilm formation in vitro, and significant alleviation of caries development in vivo under the premise of high biocompatibility. Moreover, Pc-B8 enabled effective photobleaching of tooth pigments, indicating additional potential for tooth whitening. This study presents a rationally designed Pc-AMP conjugate for non-invasive dental caries management and provides a potential strategy for optimizing dental photosensitizers.