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

Qingqing Sun, Koki Kanehira, Akiyoshi Taniguchi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)669-676
Number of pages8
JournalScience and Technology of Advanced Materials
Issue number1
Publication statusPublished - 2016 Jan 1
Externally publishedYes


  • HGFRs aggregation
  • TiO-PEG NPs
  • cell proliferation
  • cellular response
  • low-dose exposure

ASJC Scopus subject areas

  • Materials Science(all)


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