Cocktail Approach with Polyserotonin Nanoparticles and Peptides for Treatment of <i>Streptococcus mutans</i>

Dental plaque, formed by a <i>Streptococcus mutans</i> biofilm, is a major contributor to cavity formation. While antimicrobial strategies exist, the growing risk of antibiotic resistance necessitates alternative therapeutic solutions. Polyserotonin nanoparticles (PSeNPs), recently recognized for their photothermal property and promising biomedical applications, open up a new avenue for antimicrobial use. Here, we introduced a UV-initiated synthetic route for PSeNPs with improved yield. Using these PSeNPs, a cocktail treatment to reduce the viability of this cavity-causing bacteria was developed. This cocktail comprises an <i>S. mutans</i>-targeting antimicrobial peptide (GH12), an intraspecies competence-stimulating peptide that triggers altruistic cell death in <i>S. mutans</i>, and laser-activated heating of PSeNPs. The "peptide + PSeNP + laser" combination effectively inhibits <i>S. mutans</i> growth in both planktonic and biofilm states. Moreover, the cocktail approach remains effective in reducing the viability of <i>S. mutans</i> in a more virulent dual-species biofilm with <i>Candida albicans</i>. Overall, our results reinforce the utility of a multipronged therapeutic strategy to reduce cariogenic bacteria in the complex model oral biofilm.