Editorial pubs.acs.org/crt
Focus on Fundamental Materials Properties
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used nanomaterials differing in chemical composition, surface charge, and morphology (viz. graphene oxide, citrate-, and branched polyethylenimine-coated silver nanoparticles) to examine the correspondence between binding to DNA in vitro and DNA damage in lymphocytes. All three nanomaterials altered the thermal stability of DNA, producing concentrationdependent downward shifts in the melting point temperature of DNA. The rank-order of the cytotoxicity and genotoxicity (assessed as induction of micronuclei) provoked by these nanomaterials corresponded to the magnitude of their effects on DNA melting point. Control experiments with silver nitrate allowed attribution of the cytotoxicity and genotoxicity of the citrate-coated silver nanoparticles to the release of silver ions and indicated that factors other than dissolution in the exposure medium were responsible for the effects of branched polyethyeneimine-coated silver nanoparticles. In response to stress, eukaryotic cells may activate autophagy, the cellular self-digestion of organelles. and proteins.9 The review by Chatterjee et al.10 summarizes the literature on autophagy as an initial response of cells to exposure to toxic metals and metalloids, including nanoparticles. Oxidative stress induced by exposure to metal, metal oxide, and metal chalcogenide nanoparticles can trigger autophagy leading to an increase in the number of autophagosomes and the upregulation of autophagy marker proteins. Several studies have reported the presence of ENMs in autophagosomes, consistent with cellular activation of autophagy for the purpose of sequestering and degrading these materials. Autophagy may represent an adaptive cellular response to nanoparticles taken up by eukaryotic cells. The publication by Rösslein et al.11 provides a systematic analytic approach to assess in vitro toxicity of ENMs based on a cause-and-effect analysis. This procedure has been widely used in manufacturing, but this is its first application in nanotoxicology assays. This is a quantitative approach to assess the reliability and reproducibility of a widely used in vitro toxicity assay for ENMs to identify potential sources of variability using a 96-well format suitable for high-throughput screening of a wide range of target cells and organisms including bacteria and zebrafish embryos. This publication is also applicable for ecotoxicological assays because it includes a complete analysis of multiple potential confounding factors in toxicity assays using ENMs that may be responsible for contradictory results in the published literature. Chemical Research in Toxicology has compiled its published articles in the important field of nanotoxicology in a virtual issue collection in collaboration with Environmental Science & Technology and Environmental Science & Technology Letters. The collection can be viewed here: http://pubs.acs.org/page/vi/ enviro_nanotoxicology.html. We invite you to join us in the effort to accelerate nanotoxicology research by submitting your work to these journals. We hope that this collection of significant studies in nanotoxicology will advance knowledge
rowth of the nanotechnology industry has dramatically expanded the diversity of engineered nanomaterials (ENMs), and their successful commercialization raises concerns about adverse human health and environmental impacts.1 Nanotoxicology is an evolving scientific discipline that is struggling to prioritize and to develop reliable, reproducible methods for toxicity testing that address multiple caveats associated with in vitro toxicity testing of ENMs.2 Ecotoxicological testing of ENMs is especially challenging due to the wide range of potential target organisms and the complexity of natural environments, especially the aquatic environment.1 The majority of these featured papers address consideration of fundamental materials properties in the design and interpretation of in vitro toxicity screening assays that represent the first steps in a tiered approach for toxicity testing of ENMs.3 The publications by Kim et al.4 and Zhang et al.5 use carbon nanotubes as case studies. These ENMs are manufactured in large volumes for a wide range of applications, and potential adverse environmental impacts are a threat to their continued economic success.6 Carbon nanotubes vary considerably in their purity as well as in their physical and chemical properties. Kim et al.4 started with well-defined samples that were systematically modified and characterized before assessment of their in vitro toxicity. Their approach serves as a paradigm for critical assessment of specific physical and chemical properties of one category of ENMs that correlate with potential lung toxicity in an in vitro assay. A unique feature of this study was a statistical correlation analysis between material properties and cellular toxicity that identified increased surface reactivity as a major property related to the toxicity of multiwalled carbon nanotubes. Zhang et al.5 provide a comprehensive overview of various modes of interaction of carbon nanotubes with target cells and use nanocombinatorial chemistry to modulate specific interactions at the nanobio interface. This paper also emphasizes the requirement for comprehensive characterization of their multiwalled carbon nanotube library and uses highthroughput screening assays to quantify impacts of cell surface receptor binding, induction of autophagy, and modulation of cell differentiation as specific examples. This experimental approach provides a strategy for achieving the safety of ENMs by deliberate design and surface modification. The studies of Mu et al.7 and Ivansk et al.8 explored the influence of nanomaterial physicochemical properties on toxicity to human cells. Both studies point to the importance of considering nanomaterial transformation in the exposure medium. Mu et al.7 focused on zinc oxide nanomaterials and investigated the effect of polymeric coating and shape on zinc oxide dissolution and toxicity to several cell lines. An important aspect of this study was the evaluation of dissolution in exposure medium as a function of nanomaterial concentration. Analysis of experimental dissolution date using equilibrium speciation modeling revealed that cytotoxicity and DNA damage depended on ZnO solubility in cell culture medium and that nanomaterial coating and shape began to influence toxicity once the solubility limit had been exceeded. Ivask et al.8 © 2016 American Chemical Society
Published: July 18, 2016 1083
DOI: 10.1021/acs.chemrestox.6b00194 Chem. Res. Toxicol. 2016, 29, 1083−1084
Chemical Research in Toxicology
Editorial
and stimulate new collaborations and new research directions in the field.
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Joel A. Pedersen Agnes Kane AUTHOR INFORMATION
Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.
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REFERENCES
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DOI: 10.1021/acs.chemrestox.6b00194 Chem. Res. Toxicol. 2016, 29, 1083−1084
