The effect of agglomeration state of silver and titanium dioxide nanoparticles on cellular response of HepG2, A549 and THP-1 cells

Toxicol Lett. 2012 Feb 5;208(3):197-213. doi: 10.1016/j.toxlet.2011.11.006. Epub 2011 Nov 15.


Nanoparticles (NPs) occurring in the environment rapidly agglomerate and form particles of larger diameters. The extent to which this abates the effects of NPs has not been clarified. The motivation of this study was to examine how the agglomeration/aggregation state of silver (20nm and 200nm) and titanium dioxide (21nm) nanoparticles may affect the kinetics of cellular binding/uptake and ability to induce cytotoxic responses in THP1, HepG2 and A549 cells. Cellular binding/uptake, metabolic activation and cell death were assessed by the SSC flow cytometry measurements, the MTT-test and the propidium iodide assay. The three types of particles were efficiently taken up by the cells, decreasing metabolic activation and increasing cell death in all the cell lines. The magnitude of the studied endpoints depended on the agglomeration/aggregation state of particles, their size, time-point and cell type. Among the three cell lines tested, A549 cells were the most sensitive to these particles in relation to cellular binding/uptake. HepG2 cells showed a tendency to be more sensitive in relation to metabolic activation. THP-1 cells were the most resistant to all three types of particles in relation to all endpoints tested. Our findings suggest that particle features such as size and agglomeration status as well as the type of cells may contribute to nanoparticles biological impact.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death / drug effects
  • Endocytosis / drug effects
  • Flow Cytometry
  • Hep G2 Cells
  • Humans
  • Kinetics
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity*
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Particle Size
  • Silver / chemistry
  • Silver / pharmacokinetics
  • Silver / toxicity*
  • Statistics, Nonparametric
  • Titanium / chemistry
  • Titanium / pharmacokinetics
  • Titanium / toxicity*


  • titanium dioxide
  • Silver
  • Titanium