Abstract
Advances in the use of nanoparticles (NPs) has created promising progress in biotechnology and consumer-care based industry. This has created an increasing need for testing their safety and toxicity profiles. Hence, efforts to understand the cellular responses towards nanomaterials are needed. However, current methods using animal and cancer-derived cell lines raise questions on physiological relevance. In this aspect, in the current study, we investigated the use of pluripotent human embryonic stem cell- (hESCs) derived fibroblasts (hESC-Fib) as a closer representative of the in vivo response as well as to encourage the 3Rs (replacement, reduction and refinement) concept for evaluating the cytotoxic and genotoxic effects of zinc oxide (ZnO), titanium dioxide (TiO2) and silicon-dioxide (SiO2) NPs. Cytotoxicity assays demonstrated that the adverse effects of respective NPs were observed in hESC-Fib beyond concentrations of 200 µg/mL (SiO2 NPs), 30 µg/mL (TiO2 NPs) and 20 µg/mL (ZnO NPs). Flow cytometry results correlated with increased apoptosis upon increase in NP concentration. Subsequently, scratch wound assays showed ZnO (10 µg/mL) and TiO2 (20 µg/mL) NPs inhibit the rate of wound coverage. DNA damage assays confirmed TiO2 and ZnO NPs are genotoxic. In summary, hESC-Fib could be used as an alternative platform to understand toxicity profiles of metal oxide NPs.
Highlights
Advances in nanotechnology are proceeding at a striking rate and a diverse number of industrial, commercial, consumer, and health-care products have expanded by incorporating nanomaterials into these products [1,2]
In this study, we explored the potential use of human embryonic stem cell-derived fibroblasts to evaluate the cellular toxicology profiles of most common metal oxide NPs
We have shown that rod-shaped zinc oxide (ZnO) NPs at 50 μg/mL have more capacity to induce physical damage to cells leading to higher necrosis than spherical-shaped TiO2 and SiO2 NPs at 50 μg/mL
Summary
Advances in nanotechnology are proceeding at a striking rate and a diverse number of industrial, commercial, consumer, and health-care products have expanded by incorporating nanomaterials into these products [1,2]. Due to the large number, diversity, and use of NPs (nanoparticles), toxicology studies cannot keep pace. Since most of the past and current models largely depend on mammalian animals for testing, such time- and resourceintensive studies, albeit informative, cannot assess the avalanche of NP-enabled technology. Owing to differences in the toxicity profiles of the native and nano-sized counterparts, risk-assessment frameworks specific to NPs that incorporate alternative testing models have been proposed [3]. OECD guidelines and has led to calls for tiered and integrated test strategies that were used to screen and assess NPs along their chemical life cycle by in silico, in vitro and other alternative models [4]. Due to high volumes of testing and limited availability of primary human cells, cell lines of animal-origin, immortalized, and/or cancer-derived sources are commonly used for high-throughput toxicology screening studies. Since cellular immortality leads to epigenetic changes, tumorigenesis, chromosomal and genetic aberrations, the physiological relevance and reliability of cancer-derived and immortalized cell lines is limited [5,6]
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