Abstract
While the toxicity of metal-based nanoparticles (NP) has been investigated in an increasing number of studies, little is known about metal-based fibrous materials, so-called nanowires (NWs). Within the present study, the physico-chemical properties of particulate and fibrous nanomaterials based on Cu, CuO, Ni, and Ag as well as TiO2 and CeO2 NP were characterized and compared with respect to abiotic metal ion release in different physiologically relevant media as well as acellular reactivity. While none of the materials was soluble at neutral pH in artificial alveolar fluid (AAF), Cu, CuO, and Ni-based materials displayed distinct dissolution under the acidic conditions found in artificial lysosomal fluids (ALF and PSF). Subsequently, four different cell lines were applied to compare cytotoxicity as well as intracellular metal ion release in the cytoplasm and nucleus. Both cytotoxicity and bioavailability reflected the acellular dissolution rates in physiological lysosomal media (pH 4.5); only Ag-based materials showed no or very low acellular solubility, but pronounced intracellular bioavailability and cytotoxicity, leading to particularly high concentrations in the nucleus. In conclusion, in spite of some quantitative differences, the intracellular bioavailability as well as toxicity is mostly driven by the respective metal and is less modulated by the shape of the respective NP or NW.
Highlights
Engineered metal-based nanomaterials are used in many consumer products, such as textiles, electronics, or medicinal products [1–4]
All particles were investigated with respect to their specific surface area (SSA), effective density, and deposition efficiency for subsequent in vitro studies using the Distorted Grid (DG) model (Table 2)
While only minor differences were seen for acellular dissolution and abiotic oxidative reactivity detected by the ferric reduction ability of serum (FRAS) assay when comparing NP and NW of the same metal, their reactivity and dissolution are mostly driven by the respective metal under investigation
Summary
Engineered metal-based nanomaterials are used in many consumer products, such as textiles, electronics, or medicinal products [1–4]. The so-called ‘Trojan horse type’ mechanism describes an endocytotic uptake, followed by lysosomal dissolution of the metal-based materials, resulting in high metal ion concentrations within the cells. This observation has already been made for Cu-, Ag-, and Ni-based nanoparticles (NP) [16–19]. Within the present study, we comprehensively characterized particulate and fibrous metal-based nanomaterials with respect to their physicochemical properties. Besides nanomaterials known to potentially release toxic metal ions (Cu, CuO, Ni, and Ag), rather non-reactive materials (CeO2 and TiO2 ) with particulate and fibrous morphologies were included. Four different cell lines were applied to compare cytotoxicity as well as intracellular metal ion release in the cytoplasm and nucleus. Since inhalation studies are mostly performed in rats, RLE-6TN, an alveolar epithelial cell line derived from the rat lung was included as well, to compare the toxicity and bioavailability derived for human cells to rat cells
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