Assessment of CafA Targeted BAR-Encapsulated Nanoparticles against Oral Biofilms.

Porphyromonas gingivalisadherence toStreptococcus gordoniiis a crucial initial event that facilitates the colonization ofP. gingivalis, a key pathogen in periodontal disease. As such, blocking these early interactions may present a potential avenue to limitP. gingivaliscolonization. Nanoparticles encapsulating a synthetic peptide BAR (BAR-encapsulated NPs) inhibitP. gingivalis/S. gordoniibiofilm formation 1.8-fold more potently relative to free BAR. However, BAR-encapsulated NPs, like many orally delivered formulations, may benefit from a strategy that improves their retention in an open flow environment. Here, we sought to enhance the efficacy of BAR-encapsulated NPs by modifying their surfaces with coaggregation factor A (CafA), a fimbrial protein expressed by the early colonizer,Actinomyces oris. We demonstrate that the targeting moiety, CafA, enhances NP binding and exhibits specificity of adherence toS. gordonii, relative to other oral bacterial species. Furthermore, CafA-modified NPs release inhibitory concentrations of BAR for 12 h, a time frame relevant to oral dosage form delivery. Lastly, CafA-modified NPs potently inhibitP. gingivalis/S. gordoniibiofilm formation for up to 12 h and are non-toxic at therapeutically-relevant concentrations. These results suggest that CafA-modified NPs represent a novel and efficacious delivery vehicle for localized, targeted delivery of BAR toP. gingivalispreferred niches.