Gold nanoparticles as therapeutic targets against Porphyromonas gingivalis and gingivitis: A molecular docking and network pharmacology study

Functionalized gold nanoparticles exhibit a promising dual-action mechanism for treating gingivitis induced by Porphyromonas gingivalis . This study examined whether functionalized gold nanoparticles (AuNPs-PMBA) offer a dual-action approach to treating gingivitis caused by Porphyromonas gingivalis. Specifically, it investigated whether AuNPs-PMBA can both regulate host inflammation and directly suppress the pathogen. Human proteins associated with gingivitis and essential genes of Porphyromonas gingivalis were identified. Enrichment analyses and network construction helped to identify key targets using centrality metrics. Gene expression in tissue immune cells was mapped through scRNA-seq data. Finally, molecular docking of AuNPs-PMBA with the targets was performed, and their molecular interactions were analyzed. We identified key targets, including TLR4, STAT3, NLRP3, and rpoB. The enriched pathways involved cytokine–receptor interactions, neutrophil extracellular trap formation, NOD-like receptor and HIF-1 signaling, and Th17 differentiation. Single-cell data identified distinct gene signatures in neutrophils, macrophages, Th17 and regulatory T cells, B cells, and NK cells. Docking studies suggested attenuation of excessive inflammation and indicated rpoB binding, supporting a direct inhibitory effect on P. gingivalis . This study combines network pharmacology with single-cell transcriptomics to create a multi-omics framework, which is uncommon in periodontal nanotherapy and helps identify host–pathogen targets for AuNPs-PMBA. These findings substantiate the therapeutic potential of gold nanoparticles in reducing reliance on medication, mitigating resistance, and achieving targeted periodontal regeneration. This study presents a robust systems-biology framework for future translational research, focusing on personalized, multimodal interventions in periodontal disease.