self-assembled pH-responsive antibacterial nanoparticles disturb cell envelope integrity and suppress virulence factors of Streptococcus mutans.

OBJECTIVE

pH-responsive materials that could target cariogenic environment have demonstrated great potential to inhibit dental caries. The objective is to investigate the anti-caries property of the self-assembled, pH-responsive antibacterial dodecylmethylaminoethyl methacrylate nanoparticles (DMAEM NPs) and explore the antibacterial mechanism.

METHODS

DMAEM was analyzed by computational simulation. Then it was synthesized and characterized. The in-vitro cytotoxicity and pH-responsive effect were tested in various pH values. Then, the effect of DMAEM NPs on the S. mutans biofilms was investigated with a treatment mode like daily oral care (10 min, twice per day). The RNA-seq and transcriptome analysis was conducted. The biocompatibility and anti-caries effect were also investigated in a rat model.

RESULTS

. DMAEM self-assembled into nanoparticles and the morphologies varied in different pHs. The NPs demonstrated good in-vitro biosafety and acid-activated inhibiting effect on S.mutans biofilms. With repeated short-time treatment by DMAEM NPs， the biofilm activity, lactic acid production and EPS formation were inhibited. SEM and TEM images showed the bacterial cell envelops were ruptured. On the transcriptomic level, DMAEM NPs down regulated the gene expression such as gtfBC, gbpC and lrgAB. The COG, GO and KEGG analysis showed the function of ribosome and macromolecule metabolism were mainly down regulated. In the rat model, DMAEM NPs showed no side effect on oral mucosa and reduced the caries scoring.

SIGNIFICANCE: The self-assembled, pH-responsive DMAEM NPs could inhibit the cariogenic biofilm formation and the development of dental caries. This provides an interesting strategy to combat dental caries, which is promising for future application.