Zerovalent Fe, Co and Ni nanoparticle toxicity evaluated on SKOV-3 and U87 cell lines.

We have considered nanoparticles (NPs) of Fe, Co and Ni, three transition metals sharing similar chemical properties. NP dissolution, conducted by radioactive tracer method and inductively coupled plasma mass spectrometry, indicated that NiNPs and FeNPs released in the medium a much smaller amount of ions than that released by Co NPs. The two considered methodological approaches, however, gave comparable but not identical results. All NPs are readily internalized by the cells, but their quantity inside the cells is less than 5%. Cytotoxicity and gene expression experiments were performed on SKOV-3 and U87 cells. In both cell lines, CoNPs and NiNPs were definitely more toxic than FeNPs. Real-time polymerase chain reaction experiments aimed to evaluate modifications of the expression of genes involved in the cellular stress response (HSP70, MT2A), or susceptible to metal exposure (SDHB1 and MLL), or involved in specific cellular processes (caspase3, IQSEC1 and VMP1), gave different response patterns in the two cell lines. HSP70, for example, was highly upregulated by CoNPs and NiNPs, but only in SKOV-3 cell lines. Overall, this work underlines the difficulties in predicting NP toxicological properties based only on their chemical characteristics. We, consequently, think that, at this stage of our knowledge, biological effects induced by metal-based NPs should be examined on a case-by-case basis following studies on different in vitro models. Moreover, with the only exception of U87 exposed to Ni, our results suggest that metallic NPs have caused, on gene expression, similar effects to those caused by their corresponding ions.

Effects of metal(loid)-based nanomaterials on essential element homeostasis: the central role of nanometallomics for nanotoxicology.

The growing use of engineered nanomaterials in both commercial products and biomedical applications leads to increasing exposure for production line workers, consumers and patients. Therefore, the understanding of biological effects induced by nanomaterials is crucial for their safety assessment. An important group of nanomaterials is represented by metal(loid)-based nanoparticles, because of their unique physico-chemical properties. Metal(loid)-based nanoparticles themselves, the related ion release, and their nanometallomes, can potentially interact with essential elements causing dys-homeostasis and adverse biological effects. In this work, we describe the effects of metal(loid)-based nanoparticles on essential element homeostasis. In particular, we consider the most used and promising metal(loid)-based nanoparticles, highlighting that the new emerging concept of nanometallomics is important to disclose the impact of these nanoparticles on human health and the related long-term effects.

Cytotoxicity and morphological transforming potential of cobalt nanoparticles, microparticles and ions in Balb/3T3 mouse fibroblasts: an in vitro model.

We previously described the behaviour of different cobalt forms, i.e., cobalt nanoparticles (CoNP), cobalt microparticles (CoMP) and cobalt ions (Co(2+)), in culture medium (dissolution, interaction with medium components, bioavailability) as well as their uptake and intracellular distribution in Balb/3T3 mouse fibroblasts (Sabbioni, Nanotoxicology, 2012). Here, we assess the cytotoxicity and morphological transformation of CoNP compared not only to Co(2+), but also to CoMP and to released Co products. Cytotoxicity reached maximum at 4-h exposure, with ranking CoMP > CoNP > Co(2+). However, if we consider toxicity as a function of intracellular Co, toxicity of the ionic forms seems to prevail over the particles. Co forms other than Co(2+) released from particles had toxicity intermediate between particles and ions. Alterations in concentrations of essential elements (Cu, Mg, Zn) in cells exposed to Co particles may contribute to toxicity. Both CoMP and CoNP (but not Co(2+) and other released Co forms) induced morphological transformation (CoMP > CoNP). This was dependent on reactive oxygen species production and lipid peroxidation, as indicated by inhibition of type III foci with ascorbic acid. The present results suggest that the previously demonstrated massive mitochondrial and nuclear Co internalisation and DNA adduct formation by CoMP and CoNP (Sabbioni, Nanotoxicology, 2012) induce toxicity and transformation. On the contrary, the role of ions released by particles in culture medium is negligible. Thus, both the chemical and the physical properties of Co particles contribute to cytotoxicity and morphological transformation.