Toxicity of silica nanoparticles depends on size, dose, and cell type

Nanomedicine. 2015 Aug;11(6):1407-16. doi: 10.1016/j.nano.2015.03.004. Epub 2015 Mar 25.


Monodisperse spherical silica nanoparticles (SNPs) with diameters of 20-200 nm were employed to study size, dose, and cell-type dependent cytotoxicity in A549 and HepG2 epithelial cells and NIH/3T3 fibroblasts. These uniform SNPs of precisely controlled sizes eliminated uncertainties arising from mixed sizes, and uniquely allowed the probing of effects entirely size-dependent. Cell viability, membrane disruption, oxidative stress, and cellular uptake were studied. The extent and mechanism of SNP cytotoxicity were found to be not only size and dose dependent, but also highly cell type dependent. Furthermore, the 60 nm SNPs exhibited highly unusual behavior in comparison to particles of other sizes tested, implying interesting possibilities for controlling cellular activities using nanoparticles. Specifically, the 60 nm SNPs were preferentially endocytosed by cells and, at high doses, caused a disproportionate decrease in cell viability. The present work may help elucidate certain contradictions among existing results on nanoparticle-induced cytotoxicity.

From the clinical editor: Silica nanoparticles are being investigated in many research areas for their use in clinical applications. Nonetheless, the relationship between particle size and potential toxicity remains to be elucidated. In this article, the authors studied the biological effects of spherical SNPs with precise diameters between 20 and 200 nm on three different cell types and their results should provide more data on safety for better drug design.

Keywords: Cellular uptake; Cytotoxicity; Oxidative stress; Silica nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Humans
  • Mice
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nanoparticles / toxicity*
  • Particle Size
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / toxicity*


  • Silicon Dioxide