Superparamagnetic Iron Oxide Nanoparticles Protect Human Gingival Fibroblasts from Porphyromonas gingivalis Invasion and Inflammatory Stimulation.

Abstract

IntroductionModulating the inflammatory response of human gingival fibroblasts (hGFs) is important for the control of periodontal inflammation because it is a key event in the pathogenesis of periodontitis. Here, we aimed to determine whether polyglucose sorbitol carboxymethyl ether (PSC)-coated superparamagnetic iron oxide nanoparticles (SPIONs) protect hGFs against invasion and inflammatory stimulation by Porphyromonas gingivalis (P. gingivalis).MethodsFirst, we determined the cytotoxicity and antimicrobial activity of PSC-SPIONs. Then, their effects on invasion of hGFs by P. gingivalis were evaluated by counting invading P. gingivalis, fluorescence staining, and transmission electron microscopy. The effect of PSC-SPIONs on inflammation in hGFs induced by P. gingivalis lipopolysaccharide was evaluated by measurement of reactive oxygen species (ROS), and enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, and Western blotting of key indicator molecules. The effects of dimercaptosuccinic acid (DMSA)-coated SPIONs and the free form of PSC alone were also tested and compared with those of PSC-SPIONs.ResultsPSC-SPIONs (25 μg/mL) are cytocompatible with hGFs and exhibit no antimicrobial effects on P. gingivalis. However, they inhibit invasion of hGFs by P. gingivalis at 15 μg/mL. They also decrease ROS production and inflammatory cytokine secretion by hGFs at 5, 15, and 25 μg/mL, by downregulating activation of the nuclear factor-kappa B signaling pathway. Furthermore, PSC alone does not inhibit inflammation, while DMSA-SPIONs do. This indicates that the nanosize effects of PSC-SPIONs, rather than their coating material, play the dominant role in their anti-inflammatory activity.ConclusionPSC-SPIONs protect hGFs against P. gingivalis invasion and inflammatory stimulation. Thus, they have potential for clinical application in control of periodontal inflammation.