Functionalized Surface-Charged SiO₂ Nanoparticles Induce Pro-Inflammatory Responses, but Are Not Lethal to Caco-2 Cells

Abstract

Nanoparticles (NPs) are widely used in food, and analysis of their potential gastrointestinal toxicity is necessary. The present study was designed to determine the effects of silica dioxide (SiO 2 ), titanium dioxide (TiO 2 ), and zinc oxide (ZnO) NPs on cultured THP-1 monocyte-derived macrophages and human epithelial colorectal adenocarcinoma (Caco-2) cells. Exposure to ZnO NPs for 24 h increased the production of redox response species (ROS) and reduced cell viability in a dose-dependent manner in THP-1 macrophages and Caco-2 cells. Although TiO 2 and SiO 2 NPs induced oxidative stress, they showed no apparent cytotoxicity against both cell types. The effects of functionalized SiO 2 NPs on undifferentiated and differentiated Caco-2 cells were investigated using fluorescently labeled SiO 2 NPs with neutral, positive, or negative surface charge. Exposure of both types of cells to the three kinds of SiO 2 NPs significantly increased their interaction in a dose-dependent manner. The largest interaction with both types of cells was noted with exposure to more negatively surface-charged SiO 2 NPs. Exposure to either positively or negatively, but not neutrally, surface-charged SiO 2 NPs increased NO levels in differentiated Caco-2 cells. Exposure of differentiated Caco-2 cells to positively or negatively surface-charged SiO 2 NPs also upregulated interleukin-8 expression. We conclude that functionalized surface-charged SiO 2 NPs can induce pro-inflammatory responses but are noncytotoxic.

Impact of Surface Modification on Cellular Uptake and Cytotoxicity of Silica Nanoparticles

“…NPs is in agreement with our recent study, which showed better interaction of COOH-SiO2 NPs with Caco-2 cells compared with NH 2 -and OH-SiO 2 NPs[35].Confocal microscopy showed localization of OH-SiO2 NPs in the proximity of the cell membrane and less internalization of these particles in RAW264.8 macrophages. This nding suggests that OH-SiO 2 NPsinduced cell death of RAW264.8 macrophages is not necessarily through internalization of the particles, but rather the physical contact between the particles and cell membrane, in agreement with the recent nding of the cytolytic toxicity of silanol-rich SiO 2 NPs (Spyrogianni et al 2017).…”

“…NPs than OH-or NH 2 -SiO 2 NPs [35]. The present ndings and our previous study show that the difference in the extent of internalization or cytotoxicity is not explained by the differences in zeta potentials.…”

“…MTS assay was conducted using CellTiter 96® Aqueous One Solution Cell Proliferation Assay (Promega, Madison, WI) as described previously [35]…”

The toxicity of nanoparticles and their interaction with cells: an in vitro metabolomic perspective

“…Many studies used conventional essays to measure this response. 119,120,121 However, these assays can also interfere with NPs during the measurement of inflammatory response in cell lines. Some inflammatory cytokines were reported to get adsorbed on the NP surface causing an interference (Figure 7a).…”

Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models

“…Although these models are closer to the intestinal anatomy and physiology than conventional monocultures, the most used model for the evaluation of the exposure to NBMs is still the culture of Caco-2 cells on porous membrane inserts. In these conditions the cells rapidly differentiate into an intestinal barrier [ 34 – 37 ]. In addition the HCT116 model, another colon cancer cell line, is a widely accepted tool to evaluate the genotoxicity of NBMs [ 38 – 41 ].…”