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

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.

EGF Conjugation Improves Safety and Uptake Efficacy of Titanium Dioxide Nanoparticles

“…Previously, our research showed that a low concentration of TiO 2 PEG NPs induces HepG2 cells to proliferate through the HGFR receptor aggregation [ 13 ], and we have also found that TiO 2 PEG NPs can induce A431 cell proliferation [ 14 ]. These findings suggested that TiO 2 PEG NPs could increase the risk of tumor overgrowth.…”

“…Therefore, it is very beneficial to investigate the safety of TiO 2 PEG NPs as used in nanomedicine. Our previous research concluded that TiO 2 PEG NPs have a relatively low cellular uptake ratio [ 12 , 13 , 14 ]. In addition, TiO 2 PEG NPs induce HepG2 and A431 cell proliferation [ 14 ].…”

“…Previously, we investigated the interaction between TiO 2 NPs and cancer cell lines to clarify the safety and cellular uptake efficacy of TiO 2 NPs [ 12 , 13 , 14 ]. Our results showed that 100 nm TiO 2 NPs had a low cellular uptake by cancer cell lines.…”

“…Moreover, TiO 2 NPs induced HepG2 and A431 cell proliferation [ 14 ]. TiO 2 NPs can associate with hepatocyte growth factor receptors (HGFRs), leading to receptor aggregation, facilitating the recruitment of more signal transduction molecules, and HepG2 cell proliferation and growth [ 13 ]. These results suggest that TiO 2 NPs can increase the risk of tumor overgrowth while being used for PDD and PDT.…”

Insights into Theranostic Properties of Titanium Dioxide for Nanomedicine

“…However, an extensive distribution of lysosome and expression of endoplasmic reticulum proteins can be induced by anatase TiO 2 nanorods [128]. On the other hand, polymeric surface modifications can reduce or diminish hazard risks caused by the administration of TiO 2 nanomaterials [134][135][136][137]. The surface modifications may suppress the reactivity of crystals and minimize cellular and subcellular obstructive interactions [44,125,138].…”