Shikonin-Loaded Ph-Responsive Pda-Peg Msns Prevent Dental Caries

This study assessed PDA-PEG modified pH-responsive mesoporous silica nanocarriers based on shikonin (MSNs-Shikonin@PDA-PEG, MSPP) for caries prevention using in vitro and in vivo experiments. In vitro, MSPP inhibited S. mutans via microdilution, biofilm disruption, and reduced HA adhesion. In vivo, MSPP lowered caries scores (Keyes/X-ray), bacterial counts, and showed biosafety (weight/mucosa/organ assays), confirming efficacy against dental caries. MSPP demonstrated superior antibacterial activity against S. mutans (MIC: 16 μg/mL), S. sobrinus, and S. sanguinis (MIC: 8 μg/mL each) compared to MSNs. At ≤8 μg/mL, it significantly inhibited cariogenic bacterial adhesion to hydroxyapatite (4 μg/mL: ∼50% inhibition; P<0.05) and disrupted biofilm formation (16 μg/mL: strongest suppression). Live/dead staining revealed 8 μg/mL MSPP eliminated 51% of pre-existing biofilm bacteria. In rats, MSPP (8 μg/mL) reduced salivary S. mutans levels, decreased smooth surface and pit/fissure caries (Keyes scoring/X-ray), and maintained biosafety (organ coefficients/oral mucosa histology comparable to controls). These findings highlight MSPP’s dual efficacy in suppressing bacterial virulence and caries progression without toxicity, supported by dose-dependent antibacterial/anti-adhesion effects and in vivo safety validation. MSPP can effectively inhibit the growth and adhesion of major cariogenic bacteria in the planktonic state and in the biofilm state in vitro, and it safely and effectively prevented and reduced the formation and progression of caries in rats in vivo.