CafA-modified Nanoparticles Enhance Specific Targeting and Retention to Streptococcus gordonii

Objectives: Porphyromonas gingivalis adherence to Streptococcus gordonii may be important for colonization of the oral cavity by P. gingivalis. We previously showed that nanoparticles encapsulating the synthetic peptide BAR (BAR-NPs) inhibited P. gingivalis adherence more potently than free BAR. However, BAR-NPs released > 50% of encapsulated peptide within 2 hr of delivery and would exhibit low retention in an open flow environment such as the oral cavity.
Hypothesis: Targeting BAR-NPs to the streptococcal surface using the CafA protein will enhance their retention and prolong BAR release.
Methods: CafA-modified NPs encapsulating BAR peptide were synthesized using a double emulsion solvent evaporation technique. NP size was assessed using scanning electron microscopy and surface density of CafA was quantified by microBCA. The specificity and retention of CafA-modified NPs to immobilized S. gordonii was then determined. Release kinetics of BAR from modified NPs was determined using fluorescently-labeled BAR.
Results: The average diameter of CafA-modified NPs was 89.7 ± 26.3 nm and the BAR payload of NPs was 15.73 ± 1.9 ug/mg NPs under the synthetic conditions utilized. Surface density of CafA varied directly with its input concentration during NP synthesis. CafA-modified NPs bound to S. gordonii at 2.6-fold greater levels than to several other oral organisms, demonstrating specificity of adherence. CafA-modified NP adherence to S. gordonii was significantly greater than control avidin-modified NPs and 65% of the CafA-modified NPs remained bound to S. gordonii after 8 hr. Finally, CafA-modified NPs encapsulating BAR were shown to release peptide for greater than 8 hr.
Conclusions: Surface modification of BAR-NPs with CafA specifically targeted NPs to S. gordonii. Additionally, CafA-modified NPs remained bound to S. gordonii, releasing BAR for >8 hr. This suggests that CafA-modified NPs may represent a more efficacious delivery vehicle to target BAR to preferred niches of P. gingivalis in the oral cavity.