UBI29-41-targeted, NIR-triggered nanoparticles for enhanced PDT against periodontal plaque biofilm formation and immunomodulation

Periodontitis, a prevalent inflammatory disease affecting the oro-maxillofacial region, is induced by dental plaque biofilms. Periodontitis not only causes the degradation of supporting periodontal tissues but also poses a significant threat to overall health. The distinctive architecture of biofilms renders conventional mechanical debridement and antibiotic treatment ineffective against them. To overcome this problem, in this study, we successfully developed a multifunctional nanocomposite that combines antimicrobial peptides with photodynamic therapy (PDT) to selectively exert antimicrobial and anti-inflammatory effects. Our findings show that under 808-nm single-wavelength near-infrared light irradiation, the cationic antimicrobial peptide UBI29-41 not only enhances the efficacy of antibacterial PDT in specifically inhibiting the formation of periodontal biofilm by binding to lipopolysaccharide (LPS) and lipoteichoic acid (LTA) on the surface of bacteria through electrostatic interactions. Additionally, the targeting effect of UBI29-41 on LPS inhibits IκBα phosphorylation and NF-κB signaling pathway activation, ultimately exerting anti-inflammatory effects. We confirmed our in vivo findings in a rat periodontitis model and also demonstrated efficacy of the nanoparticles in inhibiting the degradation of collagen in gingival tissue, which enabled the successful treatment of periodontal disease. Hence, this study offers a novel strategy for the precise treatment of periodontal disease, including the management of deeply infected tissues.