Nanoparticle-induced molecular responses – focus on nanosilver

The rapid development of nanotechnologies has been accompanied by an increased concern for the safety of nanomaterials and consequently the number of publications on nanotoxicology has increased rapidly. However, inadequate characterization of the investigated nanomaterials has obscured risk assessment. Today, nanosilver is used in more manufacturer-identified consumer products than any other nanomaterial. A major concern is the possibility that these materials possess novel physico-chemical properties compared to the bulk counterparts. Our in vitro data suggest that the toxicity of nanosilver is comparable to that of silver ions. From a mechanistic perspective, ROS generation and oxidative stress, demonstrated by the hierarchical oxidative stress paradigm, is a generally accepted model to explain the toxic effects of various types of nanoparticles. We have previously reported that both silver ions and silver nanoparticles induce ROS, apoptosis and necrosis in A549 and THP-1 cells. This increase was found to correlate with increased gene expression of stress-related genes (e.g. HO-1 and HSP70). Additionally, global gene arrays were conducted to compare between silver ions and nanosilver. Despite significant increases in ROS levels, bulky DNA adduct levels only increased at highly cytotoxic silver concentrations whereas comet assay analysis showed no genotoxicity. Although increasing evidence suggests that nanosilver toxicity primarily is due to silver ions, the nanoparticle might exert different toxicity due to alternative uptake and intracellular dissolution. In correspondence, phagozytosing cells such as macrophages appear especially sensitive to silver nanoparticles compared to e.g. epithelial cells. These findings indicate the importance of evaluating the toxic contribution of nanoparticle dissolution.