Nanobio-interaction and nanotoxicology studies: exploring the cell toxicity mechanisms
Pierpaolo POMPA
(Italian Institute of Technology, Ehs Unit)
The increasing market and application of nanomaterials in everyday articles and tools require a deepening of their toxicological impact on human health. Among the several nanotechnologies, organic and inorganic nanoparticles rise concerns regarding their chances to enter the organism and, finally, the cells. The toxicity of nanoparticles is known to be dependent on size, shape, surface chemistry and, of course, on dose. Moreover, nanoparticles undergo dramatic changes of their physico-chemical properties once introduced in biological fluids or tissues. These changes may result in unexpected toxicological features, increasing the risks more than the expected benefits. In this perspetive, the study of toxicity mechanisms of the different nanomaterials and their specific interaction with the diverse tissues and cell types is crucial.
We have recently gained insights on silver nanoparticles (AgNPs) mechanism of cell toxicity. Ag toxicity has been known since centuries and is supported by many observations in literature. Cell death induced by AgNPs, as well as gene expression and release of inflammatory cytokines following their administration, has been also shown both in vitro and in vivo, such as in mammalians, nematodes, fishes and artropodes, but no mechanism details have been clearly proved yet. We demonstrated that cell internalization by endocytosis of AgNPs, ending in the endo-lysosomal compartments, leads to detrimental effects for the cell. The toxic potential of fully characterized AgNPs in two cell lines derived from different tissues, namely, HeLa and A549 cells has been clearly quantified. By the use of an Ag+ ion-specific fluorescent probe, we observed the intracellular release of Ag+ ions in living cells after nanoparticle internalization, underlying that in-situ particle degradation is promoted by the acidic lysosomal environment. Furthermore, the activation of metallothioneins in response to AgNPs and the possibility to reverse the main toxic pathway by Ag+ chelating agents demonstrate a cause/effect relationship between ions and cell death. The impact of AgNPs degraded in the lysosomes and the following release of Ag+ ions in the cytosol induces cell damages, while ions released in the cell culture medium play a negligible effect. These detailed findings will be useful to develop safer-by-design nanoparticles and proper regulatory guidelines of AgNPs.
