In Vitro Cytotoxicity And Apoptosis-Induction Of Silica Nanoparticles In Human Hepatoma HepG2 Cells

Due to simple structure, SiO2 nanoparticles (SNP) are easy to produce and be modified by functional groups, making them appealing for designs for different applications. In recent years, SNP have not only been widely used in industrial fields, but in biomedical fields such as diagnosis, imaging, drug carrier etc. SNP have been discovered to exert cytotoxicity and apoptosis-induction in some human normal cells. But up to now, seldom studies have focused on the cytotoxicity of SNPs in the tumor cells.In this paper, the cytotoxicity of SNP within 7-50 nm and the related mechanism were investigated in human hepatoma HepG2 model cells, with the normal human hepatocyte cell L-02 as control. The results showed that the anti-tumor activity of SNP strongly depended on the particle size of SNP, and the efficacies of the anti-proliferation decreased in the order of 20-nm>7-nm>50-nm. Also, SNP produced cytotoxicities in the typical dose-and time-dependent manners. The cell viability of HepG2 cells decreased to 18.5% after 72h incubation with 160μg/ml 20 nm-SNP. But in L-02 cells, only 20 nm-and 7 nm-SNP showed slight toxicity when their concentrations reached 320 and 640μg/ml. In comparison to L-02cells, it is easier for SNP to locate in the cytoplasm and inside the nucleuses of HepG2 cells and then induce apoptosis. Moreover, in HepG2 cells, oxidative stress and apoptosis were induced after exposure to 7 nm-and 20 nm-SiO2. The caspase-3 activity and p53 expression was increased, Bcl-2 and procaspase-9 was decreased in dose-dependent patterns, whereas the expression of Bax was not significantly changed. Based on these results, it can be concluded that a mitochondrial-dependent pathway triggered by ROS-mediated oxidative stress may be involved in the SNPs-induced apoptosis and thus the cytotoxicity in human hepatic cancer cell HepG2.In addition, the most active 20 nm-SNP was cationically modified to obtain 6 batches of SNP withζpotentials ranging from-22.1-+44.16mV. Among them, SNP20 (-22.1 mV), SNP20a (-8.93 mV), SNP20b (-0.70 mV) and SNP20c (+4.16 mV) were chosen to study their cytotoxicity and apoptosis-induction in human hepatoma HepG2 Cells. The results showed that the anti-tumor activity of these different SNPs is slightly different. And a similar trend in the apoptosis-induction in HepG2 cells was also detected by the following flow cytometer analysis. It indicated thatζpotential of the SNPs might be related with their anti-tumor activity.