Effect of titanium dioxide nanoparticle on proliferation, drug-sensitivity, inflammation, and metabolomic profiling of human oral cells

Rene Garcia-Contreras, Rogelio J. Scougall-Vilchis, Rosalia Contreras-Bulnes, Masahiro Sugimoto, Hiroshi Nakajima, Hiroshi Sakagami

Research output: Chapter in Book/Report/Conference proceedingChapter


Although titanium dioxide nanoparticles (TiO2 NPs) improve mechanical and antibacterial properties of conventional glass ionomer cements (GIC), their biocompatibility is still controversial. Most of the previous studies of TiO2 NP toxicity have been done using animal models or nonoral tissue cells. We initiated a series of studies to show how TiO2 NPs affect viability, inflammation, and drug sensitivity in human malignant and nonmalignant cells derived from the oral cavity. TiO2 NPs did not affect the cytotoxicity of representative anticancer drugs (doxorubicin, melphalan, 5-FU, docetaxel, gefitinib) against squamous carcinoma cell lines, but significantly stimulated PGE2 production and COX-1/COX-2 protein expression by gingival fibroblasts in synergy with interleukin-1β (IL-1β). TiO2 NPs slightly stimulated the proliferation of gingival fibroblasts (possibly for repair synthesis), and also enhanced GIC-induced PGE2 production, suggesting a possible link between inflammation and hormesis. TiO2 NPs, once endocytosed into vacuoles, reduced cellular intermediate molecules of the urea cycle and polyamine, S-adenosylmethionine, and glutathione synthetic pathways. TiO2 NPs further enhanced the IL-1β effects on cellular metabolites. Based on these experimental evidences, we recommend that dental materials containing TiO2 NPs for patients with gingivitis or periodontitis should be used carefully. Metabolomics analysis may be useful to elucidate the mechanism of inflammation induction and explore the therapeutic strategy for gingivitis and periodontitis.

Original languageEnglish
Title of host publicationNanobiomaterials in Dentistry
Subtitle of host publicationApplications of Nanobiomaterials
PublisherElsevier Inc.
Number of pages29
ISBN (Electronic)9780323428903
ISBN (Print)9780323428675
Publication statusPublished - 2016 Jun 13


  • Cytotoxicity
  • Glass ionomer cements
  • Inflammation
  • Metabolomic analysis
  • TiO NPs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Engineering(all)


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