Global Proteomics to Study Silica Nanoparticle-Induced Cytotoxicity and Its Mechanisms in HepG2 Cells

Abstract

Silica nanoparticles (SiO2 NPs) are commonly used in medical and pharmaceutical fields. Research into the cytotoxicity and overall proteomic changes occurring during initial exposure to SiO2 NPs is limited. We investigated the mechanism of toxicity in human liver cells according to exposure time [0, 4, 10, and 16 h (h)] to SiO2 NPs through proteomic analysis using mass spectrometry. SiO2 NP-induced cytotoxicity through various pathways in HepG2 cells. Interestingly, when cells were exposed to SiO2 NPs for 4 h, the morphology of the cells remained intact, while the expression of proteins involved in mRNA splicing, cell cycle, and mitochondrial function was significantly downregulated. These results show that the toxicity of the nanoparticles affects protein expression even if there is no change in cell morphology at the beginning of exposure to SiO2 NPs. The levels of reactive oxygen species changed significantly after 10 h of exposure to SiO2 NPs, and the expression of proteins associated with oxidative phosphorylation, as well as the immune system, was upregulated. Eventually, these changes in protein expression induced HepG2 cell death. This study provides insights into cytotoxicity evaluation at early stages of exposure to SiO2 NPs through in vitro experiments.

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

“…Some in vivo and in vitro studies have shown that SiO 2 NPs can cause toxicity to different organs in the human body; toxicity has been demonstrated in lung epithelial cells [ 9 ], liver cells [ 10 ], intestinal cells [ 11 ], the lungs [ 12 ], and kidneys [ 13 ]. In addition, SiO 2 NPs were found to induce genotoxicity and alterations in gene and protein expression [ 12 , 14 ], and Chen et al [ 15 ] reported that SiO 2 NPs can induce cornea toxicity.…”

Using NAMs to characterize chemical bioactivity at the transcriptomic, proteomic and phosphoproteomic levels

“…The quality control showed high quality of the data with the number of detected transcripts, proteins and phosphosites summarized in Table S1. The number of detected proteins (over 8,000) and phosphosites (over 47,000) were at the upper end of those previously reported 50,51 highlighting the improvements and breadth in coverage now possible for robust toxico-proteomic analysis.…”

In vitro toxicity screening of amorphous silica nanoparticles using mitochondrial fraction exposure followed by MS-based proteomic analysis

“…9 Also, the findings from this study are consistent with the report from Lee et al (2021) on mitochondrial effects after the exposure of HepG2 cells to a single nanosilica material and following proteomics changes. 59 Besides, mitochondrial exposure involves a relatively shorter exposure time and less material for exposure, compared with exposure of cells to these SiNPs. To our knowledge, very limited work on the application of proteomics for this purpose has thus far been done on these nanomaterials, and none on the toxicity testing of nanoforms.…”