Silica nanoparticles induce autophagy and autophagic cell death in HepG2 cells triggered by reactive oxygen species

J Hazard Mater. 2014 Apr 15:270:176-86. doi: 10.1016/j.jhazmat.2014.01.028. Epub 2014 Jan 24.


Silica nanoparticles (SNPs) are becoming favorable carriers for drug delivery or gene therapy, and in turn, the toxic effect of SNPs on biological systems is gaining attention. Currently, autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials, yet there have been scarcely research about the mechanisms of autophagy and autophagic cell death associated with SNPs. In this study, we verified the activation of SNPs-induced autophagy via the MDC-staining and LC3-I/LC3-II conversion, resulted in a dose-dependent manner. The typically morphological characteristics (autophagosomes and autolysosomes) of the autophagy process were observed in TEM ultrastructural analysis. In addition, the autophagic cell death was evaluated by cellular co-staining assay. And the underlying mechanisms of autophagy and autophagic cell death were performed using the intracellular ROS detection, autophagy inhibitor and ROS scavenger. Results showed that the elevated ROS level was in line with the increasing of autophagy activation, while both the 3-MA and NAC inhibitors effectively suppressed the autophagy and cell death induced by SNPs. In summary, our findings demonstrated that the SNPs-induced autophagy and autophagic cell death were triggered by the ROS generation in HepG2 cells, suggesting that exposure to SNPs could be a potential hazardous factor for maintaining cellular homeostasis.

Keywords: Autophagic cell death; Autophagy; Nanotoxicity; Reactive oxygen species; Silica nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / drug effects
  • Cell Survival / drug effects
  • Hep G2 Cells
  • Humans
  • Microscopy, Electron, Transmission
  • Nanoparticles / toxicity*
  • Nanoparticles / ultrastructure
  • Reactive Oxygen Species / metabolism*
  • Silicon Dioxide / toxicity*


  • Reactive Oxygen Species
  • Silicon Dioxide