Special Issue "Toxicity and Ecotoxicity Assessment of Nanomaterials by In Vitro Models"

A special issue of Nanomaterials (ISSN 2079-4991).

Deadline for manuscript submissions: closed (31 January 2020).

Special Issue Editors

Dr. Marie Carriere
E-Mail Website
Guest Editor
Université Grenoble Alpes, CEA, INAC/SyMMES, Grenoble, France
Interests: Toxicity of nanomaterials on in vitro models of lung and intestine; physico-chemical characterization of nanomaterial properties and fate; safer-by-design approach
Dr. Camille Larue
E-Mail Website
Guest Editor
CNRS, Universite de Toulouse, ECOLAB, Toulouse, France
Interests: Environmental toxicology; plants exposed to nanomaterials; spectroscopy

Special Issue Information

Dear Colleagues,

In the past few decades, significant effort has been devoted to the evaluation of toxicity and ecotoxicity of nanomaterials (NMs), particularly using in vitro models and methods. These models and methods are particularly well suited to explore the mode of action and molecular mechanisms of NM toxicity, but extrapolation to an in vivo situation is sometimes difficult to achieve. Moreover, in vitro systems often suffer from dramatic interference of NMs with assay processes and components.

This Special Issue will cover recent advances in the in vitro development (and use) of cheap and robust assays for NM toxicology assessment, as well as the development of new models that better mimic the in vivo situation, including 3D cell and/or organoid models and long-term/low-dose exposure scenarios. Models that better mimic the environment, such as mesocosms, or systems encompassing soil and plants or soil, bacteria, and plants, and the flow and fate of NMs in these systems are also included. Finally, any in vitro study describing mechanistic insight into the toxicological and ecotoxicological mode of action of NMs, which may be either potential environmental pollutants, nanodrug systems, or nanobiomaterials, is also in the scope of this Special Issue.

Dr. Marie Carriere
Dr. Camille Larue
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nanotoxicology
  • nanoecotoxicology
  • in vitro models and methods
  • 3D cell culture
  • mesocosms
  • mechanistic studies

Published Papers (7 papers)

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Research

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Open AccessArticle
Quantitative Flow Cytometric Evaluation of Oxidative Stress and Mitochondrial Impairment in RAW 264.7 Macrophages after Exposure to Pristine, Acid Functionalized, or Annealed Carbon Nanotubes
Nanomaterials 2020, 10(2), 319; https://doi.org/10.3390/nano10020319 - 13 Feb 2020
Abstract
Conventional nanotoxicological assays are subjected to various interferences with nanoparticles and especially carbon nanotubes. A multiparametric flow cytometry (FCM) methodology was developed here as an alternative to quantify oxidative stress, mitochondrial impairment, and later cytotoxic and genotoxic events. The experiments were conducted on [...] Read more.
Conventional nanotoxicological assays are subjected to various interferences with nanoparticles and especially carbon nanotubes. A multiparametric flow cytometry (FCM) methodology was developed here as an alternative to quantify oxidative stress, mitochondrial impairment, and later cytotoxic and genotoxic events. The experiments were conducted on RAW264.7 macrophages, exposed for 90 min or 24 h-exposure with three types of multiwalled carbon nanotubes (MWCNTs): pristine (Nanocyl™ CNT), acid functionalized (CNTf), or annealed treatment (CNTa). An original combination of reactive oxygen species (ROS) probes allowed the simultaneous quantifications of broad-spectrum ROS, superoxide anion (O2•−), and hydroxyl radical (•OH). All MWCNTs types induced a slight increase of broad ROS levels regardless of earlier antioxidant catalase activity. CNTf strongly stimulated the O2•− production. The •OH production was downregulated for all MWCNTs due to their scavenging capacity. The latter was quantified in a cell-free system by electron paramagnetic resonance spectroscopy (EPR). Further FCM-based assessment revealed early biological damages with a mitochondrial membrane potential collapse, followed by late cytotoxicity with chromatin decondensation. The combined evaluation by FCM analysis and cell-free techniques led to a better understanding of the impacts of MWCNTs surface treatments on the oxidative stress and related biological response. Full article
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Open AccessArticle
Influences of Nanoparticles Characteristics on the Cellular Responses: The Example of Iron Oxide and Macrophages
Nanomaterials 2020, 10(2), 266; https://doi.org/10.3390/nano10020266 - 05 Feb 2020
Abstract
Iron oxide nanoparticles/microparticles are widely present in a variety of environments, e.g., as a byproduct of steel and iron degradation, as, for example, in railway brakes (e.g., metro station) or in welding fumes. As all particulate material, these metallic nanoparticles are taken up [...] Read more.
Iron oxide nanoparticles/microparticles are widely present in a variety of environments, e.g., as a byproduct of steel and iron degradation, as, for example, in railway brakes (e.g., metro station) or in welding fumes. As all particulate material, these metallic nanoparticles are taken up by macrophages, a cell type playing a key role in the innate immune response, including pathogen removal phagocytosis, secretion of free radical species such as nitric oxide or by controlling inflammation via cytokine release. In this paper, we evaluated how macrophages functions were altered by two iron based particles of different size (100 nm and 20 nm). We showed that at high, but subtoxic concentrations (1 mg/mL, large nanoparticles induced stronger perturbations in macrophages functions such as phagocytic capacity (tested with fluorescent latex microspheres) and the ability to respond to bacterial endotoxin lipopolysaccharide stimulus (LPS) in secreting nitric oxide and pro-cytokines (e.g., Interleukin-6 (IL-6) and Tumor Necrosis Factor (TNF)). These stronger effects may correlate with an observed stronger uptake of iron for the larger nanoparticles. Full article
Open AccessArticle
Protein Corona Composition of Silica Nanoparticles in Complex Media: Nanoparticle Size does not Matter
Nanomaterials 2020, 10(2), 240; https://doi.org/10.3390/nano10020240 - 29 Jan 2020
Abstract
Biomolecules, and particularly proteins, bind on nanoparticle (NP) surfaces to form the so-called protein corona. It is accepted that the corona drives the biological distribution and toxicity of NPs. Here, the corona composition and structure were studied using silica nanoparticles (SiNPs) of different [...] Read more.
Biomolecules, and particularly proteins, bind on nanoparticle (NP) surfaces to form the so-called protein corona. It is accepted that the corona drives the biological distribution and toxicity of NPs. Here, the corona composition and structure were studied using silica nanoparticles (SiNPs) of different sizes interacting with soluble yeast protein extracts. Adsorption isotherms showed that the amount of adsorbed proteins varied greatly upon NP size with large NPs having more adsorbed proteins per surface unit. The protein corona composition was studied using a large-scale label-free proteomic approach, combined with statistical and regression analyses. Most of the proteins adsorbed on the NPs were the same, regardless of the size of the NPs. To go beyond, the protein physicochemical parameters relevant for the adsorption were studied: electrostatic interactions and disordered regions are the main driving forces for the adsorption on SiNPs but polypeptide sequence length seems to be an important factor as well. This article demonstrates that curvature effects exhibited using model proteins are not determining factors for the corona composition on SiNPs, when dealing with complex biological media. Full article
Open AccessArticle
Repeated vs. Acute Exposure of RAW264.7 Mouse Macrophages to Silica Nanoparticles: A Bioaccumulation and Functional Change Study
Nanomaterials 2020, 10(2), 215; https://doi.org/10.3390/nano10020215 - 27 Jan 2020
Abstract
Synthetic amorphous silica is used in various applications such as cosmetics, food, or rubber reinforcement. These broad uses increase human exposure, and thus the potential risk related to their short- and long-term toxicity for both consumers and workers. These potential risks have to [...] Read more.
Synthetic amorphous silica is used in various applications such as cosmetics, food, or rubber reinforcement. These broad uses increase human exposure, and thus the potential risk related to their short- and long-term toxicity for both consumers and workers. These potential risks have to be investigated, in a global context of multi-exposure, as encountered in human populations. However, most of the in vitro research on the effects of amorphous silica has been carried out in an acute exposure mode, which is not the most relevant when trying to assess the effects of occupational exposure. As a first step, the effects of repeated exposure of macrophages to silica nanomaterials have been investigated. The experiments have been conducted on in vitro macrophage cell line RAW264.7 (cell line from an Abelson murine leukemia virus-induced tumor), as this cell type is an important target cell in toxicology of particulate materials. The bioaccumulation of nanomaterials and the persistence of their effects have been studied. The experiments carried out include the viability assay and functional tests (phagocytosis, NO and reactive oxygen species dosages, and production of pro- and anti-inflammatory cytokines) using flow cytometry, microscopy and spectrophotometry. Accumulation of silica nanoparticles (SiO2 NP) was observed in both exposure scenarii. However, differences in the biological effects between the exposure scenarii have also been observed. For phagocytosis, NO production and Tumor Necrosis Factor (TNF) release, repeated exposure tended to induce fewer effects than acute exposure. Nevertheless, repeated exposure still induces alterations in the macrophage responses and thus represents a scenario to be tested in detail. Full article
Open AccessArticle
Toxicological Assessment of ITER-Like Tungsten Nanoparticles Using an In Vitro 3D Human Airway Epithelium Model
Nanomaterials 2019, 9(10), 1374; https://doi.org/10.3390/nano9101374 - 25 Sep 2019
Abstract
The International Thermonuclear Experimental Reactor (ITER) is an international project aimed at the production of carbon-free energy through the use of thermonuclear fusion. During ITER operation, in case of a loss-of-vacuum-accident, tungsten nanoparticles (W-NPs) could potentially be released into the environment and induce [...] Read more.
The International Thermonuclear Experimental Reactor (ITER) is an international project aimed at the production of carbon-free energy through the use of thermonuclear fusion. During ITER operation, in case of a loss-of-vacuum-accident, tungsten nanoparticles (W-NPs) could potentially be released into the environment and induce occupational exposure via inhalation. W-NPs toxicity was evaluated on MucilAir™, a 3D in vitro cell model of the human airway epithelium. MucilAir™ was exposed for 24 h to metallic ITER-like milled W-NPs, tungstate (WO42−) and tungsten carbide cobalt particles alloy (WC-Co). Cytotoxicity and its reversibility were assessed using a kinetic mode up to 28 days after exposure. Epithelial tightness, metabolic activity and interleukin-8 release were also evaluated. Electron microscopy was performed to determine any morphological modification, while mass spectrometry allowed the quantification of W-NPs internalization and of W transfer through the MucilAir™. Our results underlined a decrease in barrier integrity, no effect on metabolic activity or cell viability and a transient increase in IL-8 secretion after exposure to ITER-like milled W-NPs. These effects were associated with W-transfer through the epithelium, but not with intracellular accumulation. We have shown that, under our experimental conditions, ITER-like milled W-NPs have a minor impact on the MucilAir™ in vitro model. Full article
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Open AccessArticle
Molecular Responses in THP-1 Macrophage-Like Cells Exposed to Diverse Nanoparticles
Nanomaterials 2019, 9(5), 687; https://doi.org/10.3390/nano9050687 - 02 May 2019
Abstract
In the body, engineered nanoparticles (NPs) may be recognized and processed by immune cells, among which macrophages play a crucial role. We evaluated the effects of selected NPs [NM-100 (TiO2), NM-110 (ZnO), NM-200 (SiO2), and NM-300 K (Ag)] on [...] Read more.
In the body, engineered nanoparticles (NPs) may be recognized and processed by immune cells, among which macrophages play a crucial role. We evaluated the effects of selected NPs [NM-100 (TiO2), NM-110 (ZnO), NM-200 (SiO2), and NM-300 K (Ag)] on THP-1 macrophage-like cells. The cells were exposed to subcytotoxic concentrations of NPs (1–25 µg/mL) and the expression of immunologically relevant genes (VCAM1, TNFA, CXCL8, ICAM1, CD86, CD192, and IL1B) was analyzed by RT-qPCR. The expression of selected cytokines, growth factors and surface molecules was assessed by flow cytometry or ELISA. Generation of reactive oxygen species and induction of DNA breaks were also analyzed. Exposure to diverse NPs caused substantially different molecular responses. No significant effects were detected for NM-100 treatment. NM-200 induced production of IL-8, a potent attractor and activator of neutrophils, growth factors (VEGF and IGF-1) and superoxide. NM-110 triggered a proinflammatory response, characterized by the activation of transcription factor NF-κB, an enhanced production of proinflammatory cytokines (TNF-α) and chemokines (IL-8). Furthermore, the expression of cell adhesion molecules VCAM-1 and ICAM-1 and hepatocyte growth factor (HGF), as well as superoxide production and DNA breaks, were affected. NM-300 K enhanced IL-8 production and induced DNA breaks, however, it decreased the expression of chemokine receptor (CCR2) and CD86 molecule, indicating potential immunosuppressive activity. The toxicity of ZnO and Ag NPs was probably caused by their intracellular dissolution, as indicated by transmission electron microscopy imaging. The observed effects in macrophages might further influence both innate and adaptive immune responses by promoting neutrophil recruitment via IL-8 release and enhancing the adhesion and stimulation of T cells by VCAM-1 and ICAM-1 expression. Full article
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Review

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Open AccessReview
Genotoxicity of Silver Nanoparticles
Nanomaterials 2020, 10(2), 251; https://doi.org/10.3390/nano10020251 - 31 Jan 2020
Abstract
Silver nanoparticles (AgNPs) are widely used in diverse sectors such as medicine, food, cosmetics, household items, textiles and electronics. Given the extent of human exposure to AgNPs, information about the toxicological effects of such products is required to ensure their safety. For this [...] Read more.
Silver nanoparticles (AgNPs) are widely used in diverse sectors such as medicine, food, cosmetics, household items, textiles and electronics. Given the extent of human exposure to AgNPs, information about the toxicological effects of such products is required to ensure their safety. For this reason, we performed a bibliographic review of the genotoxicity studies carried out with AgNPs over the last six years. A total of 43 articles that used well-established standard assays (i.e., in vitro mouse lymphoma assays, in vitro micronucleus tests, in vitro comet assays, in vivo micronucleus tests, in vivo chromosome aberration tests and in vivo comet assays), were selected. The results showed that AgNPs produce genotoxic effects at all DNA damage levels evaluated, in both in vitro and in vivo assays. However, a higher proportion of positive results was obtained in the in vitro studies. Some authors observed that coating and size had an effect on both in vitro and in vivo results. None of the studies included a complete battery of assays, as recommended by ICH and EFSA guidelines, and few of the authors followed OECD guidelines when performing assays. A complete genotoxicological characterization of AgNPs is required for decision-making. Full article
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