Low doses of TiO2-polyethylene glycol nanoparticles stimulate proliferation of hepatocyte cells

Qingqing Sun; Koki Kanehira; Akiyoshi Taniguchi

doi:10.1080/14686996.2016.1239499

Low doses of TiO₂-polyethylene glycol nanoparticles stimulate proliferation of hepatocyte cells

Sci Technol Adv Mater. 2016 Oct 17;17(1):669-676. doi: 10.1080/14686996.2016.1239499. eCollection 2016.

Authors

Qingqing Sun¹, Koki Kanehira², Akiyoshi Taniguchi¹

Affiliations

¹ Cellular Functional Nanobiomaterials Group, Research Center for Functional Materials, National Institute for Materials Science, Tsukuba, Japan; Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
² Biotechnology Group, TOTO Ltd. Research Institute , Chigasaki , Japan.

Abstract

This paper describes the effect of low concentrations of 100 nm polyethylene glycol-modified TiO₂ nanoparticles (TiO₂-PEG NPs) on HepG2 hepatocellular carcinoma cells. Proliferation of HepG2 cells increased significantly when the cells were exposed to low doses (<100 μg ml^-1) of TiO₂-PEG NPs. These results were further confirmed by cell counting experiments and cell cycle assays. Cellular uptake assays were performed to determine why HepG2 cells proliferate with low-dose exposure to TiO₂-PEG NPs. The results showed that exposure to lower doses of NPs led to less cellular uptake, which in turn decreased cytotoxicity. We therefore hypothesized that TiO₂-PEG NPs could affect the activity of hepatocyte growth factor receptors (HGFRs), which bind to hepatocyte growth factor and stimulate cell proliferation. The localization of HGFRs on the surface of the cell membrane was detected via immunofluorescence staining and confocal microscopy. The results showed that HGFRs aggregate after exposure to TiO₂-PEG NPs. In conclusion, our results indicate that TiO₂-PEG NPs have the potential to promote proliferation of HepG2 cells through HGFR aggregation and suggest that NPs not only exhibit cytotoxicity but also affect cellular responses.

Keywords: 211 Scaffold / Tissue engineering / Drug delivery; 30 Bio-inspired and biomedical materials; HGFRs aggregation; TiO2-PEG NPs; cell proliferation; cellular response; low-dose exposure.