Cytotoxic effect of silica nanoparticles against hepatocellular carcinoma cells through necroptosis induction

Abstract

Hepatocellular carcinoma (HCC) is a common cancer that affects people worldwide with high morbidity and mortality, and its resistance to current chemotherapeutic drugs is a serious concern. Cytotoxicity of silica nanoparticles (Nano-SiO2) towards cancer cells has been reported previously, but the specific mechanism is not fully clear. In this study, Nano-SiO2 showed a remarkable cytotoxic effect against HCC cells, regardless of whether the cells were drug resistant or not. Further study showed that Nano-SiO2 treatment leads to cell cycle arrest, apoptosis enhancement and necroptosis induction in the HCC cells. RNA-seq data, together with bioinformatics analysis, revealed that a series of genes involved in cancer cell death could be regulated by Nano-SiO2, among which ZBP-1 was up-regulated the most by Nano-SiO2 treatment. The siRNA based experiments demonstrated that ZBP-1 might play a key role in mediating Nano-SiO2 cytotoxic functions against HCC cells. These results have evidently signified the anti-tumor potential of Nano-SiO2 in the treatment of HCC.

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

“…The analysis of intracellular changes in HepG2 that occurred 16 h after exposure to SiO 2 NPs allowed a closer look at the mechanisms of early cytotoxicity. When SiO 2 NPs are exposed to cells for longer periods, the cells eventually die through a cytotoxic pathway, such as autophagy [ 60 , 61 ], apoptosis [ 9 , 62 , 63 ], lysosome-induced cell death [ 47 , 50 ], and necrosis [ 10 , 30 , 64 ] ( Figure 7 ). Although this study focused on global changes in the early stages of nanoparticle exposure, we expect that proteomic analysis following a future separate organelle-based study will enable a deeper understanding of the molecular processes underlying their cytotoxicity and eventuating in SiO 2 NP-induced cell death.…”

Nanomedicine in Hepatocellular Carcinoma: A New Frontier in Targeted Cancer Treatment

“…Along with that, selectively targeting tumoral hepatocytes defines another obstacle. Therefore, a selectively targeted therapy is desirable in order to selectively target the affected cells while reducing the toxicity of the therapy [48] [108][109][110][111][112][113][114][115][116][117][118], silver NPs [119][120][121][122], zinc oxide NPs [123], etc. [47].…”

All Roads Lead to the Liver: Metal Nanoparticles and Their Implications for Liver Health

“…[125] 30 nm silicon dioxide NPs were tested on patient-derived HCC primary cell lines together with adjacent primary non-HCC cell lines and showed greater cytotoxicity toward the HCC cells. [126] Intriguingly, a number of these lines were further found to be resistant to first-line antihepatoma drugs, suggesting that silicon dioxide NP therapy may be an alternate route to combat drug resistant HCC. HCC cell lines were also twice as sensitive to silicon dioxide NP treatment as a regular hepatocyte line.…”