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Cytotoxicity and Genotoxicity of Nanomaterials

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A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (20 June 2021) | Viewed by 38070

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Dr. Vanessa Valdiglesias

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Grupo NanoToxGen, Centro de Investigacións Científicas Avanzadas (CICA), Departmento de Biología, Universidade da Coruña, A Coruña, Spain
Interests: toxicology; nanotoxicology; emerging pollutants; genetics; biomarkers; mutagenesis; environmental exposure; occupational exposure
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Dear Colleagues,

The small size of nanomaterials (NM), with a size between 1 and 100 nm, gives them very particular physicochemical properties, mainly related to their increased surface area and reactivity, which makes them enormously useful for a number of applications in many different fields (biomedicine, environmental remediation, construction, electronics, hygiene and cosmetics, textile industry, etc.). However, also because of this reduced size, there are increasing concerns as to the potential adverse human health and environmental effects that the production and subsequent exposure to NM might pose. Exposure to NM indeed constitutes an emerging potential risk, mainly because the possible toxic effects of NM have not been characterized yet and, given their new properties, it is quite possible that they differ markedly from those of the same material at a larger scale. In this frame, approaches aimed at revealing or discarding the possible toxicity of NM, particularly those at the cellular and molecular levels, are essential to understand the potential risks to human health associated with their exposure and to ensure proper regulation of the production and use of these materials.

Accordingly, potential topics for this Special Issue include but are not limited to:

Genotoxicity of nanomaterials;
Cytotoxic effects of nanomaterials;
DNA repair alterations induced by nanomaterial exposure;
Interference of nanomaterials with genotoxicity/cytotoxicity testing protocols;
Standardization of new techniques for nanogenotoxicology assessment;
Alternative methods for in vitro nanotoxicology screening.

Dr. Vanessa Valdiglesias
Guest Editor

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Keywords

genotoxicity
cytotoxicity
DNA repair
standardization
alternative methods

Published Papers (12 papers)

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Editorial

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3 pages, 186 KiB

Open AccessEditorial

Cytotoxicity and Genotoxicity of Nanomaterials

by Vanessa Valdiglesias

Nanomaterials 2022, 12(4), 634; https://0-doi-org.brum.beds.ac.uk/10.3390/nano12040634 - 14 Feb 2022

Cited by 4 | Viewed by 1765

Abstract

Nanomaterials (NMs) are of significant relevance due to their unique physicochemical properties, which have been extensively exploited for widespread applications in human healthcare and consumer goods, such as cosmetics and textiles [...] Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

Research

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17 pages, 3060 KiB

Open AccessEditor’s ChoiceArticle

Graphene Oxide and Reduced Graphene Oxide Nanoflakes Coated with Glycol Chitosan, Propylene Glycol Alginate, and Polydopamine: Characterization and Cytotoxicity in Human Chondrocytes

by Lorenzo Vannozzi, Enrico Catalano, Madina Telkhozhayeva, Eti Teblum, Alina Yarmolenko, Efrat Shawat Avraham, Rajashree Konar, Gilbert Daniel Nessim and Leonardo Ricotti

Nanomaterials 2021, 11(8), 2105; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11082105 - 19 Aug 2021

Cited by 18 | Viewed by 3899

Abstract

Recently, graphene and its derivatives have been extensively investigated for their interesting properties in many biomedical fields, including tissue engineering and regenerative medicine. Nonetheless, graphene oxide (GO) and reduced GO (rGO) are still under investigation for improving their dispersibility in aqueous solutions and their safety in different cell types. This work explores the interaction of GO and rGO with different polymeric dispersants, such as glycol chitosan (GC), propylene glycol alginate (PGA), and polydopamine (PDA), and their effects on human chondrocytes. GO was synthesized using Hummer’s method, followed by a sonication-assisted liquid-phase exfoliation (LPE) process, drying, and thermal reduction to obtain rGO. The flakes of GO and rGO exhibited an average lateral size of 8.8 ± 4.6 and 18.3 ± 8.5 µm, respectively. Their dispersibility and colloidal stability were investigated in the presence of the polymeric surfactants, resulting in an improvement in the suspension stability in terms of average size and polydispersity index over 1 h, in particular for PDA. Furthermore, cytotoxic effects induced by coated and uncoated GO and rGO on human chondrocytes at different concentrations (12.5, 25, 50 and 100 µg/mL) were assessed through LDH assay. Results showed a concentration-dependent response, and the presence of PGA contributed to statistically decreasing the difference in the LDH activity with respect to the control. These results open the way to a potentially safer use of these nanomaterials in the fields of cartilage tissue engineering and regenerative medicine. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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13 pages, 1026 KiB

Open AccessFeature PaperArticle

Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA Damage

by Vanessa Valdiglesias, Natalia Fernández-Bertólez, Carlota Lema-Arranz, Raquel Rodríguez-Fernández, Eduardo Pásaro, Ana Teresa Reis, João Paulo Teixeira, Carla Costa and Blanca Laffon

Nanomaterials 2021, 11(8), 1930; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11081930 - 27 Jul 2021

Cited by 5 | Viewed by 2137

Abstract

Metal oxide nanoparticles (NPs) have a wide variety of applications in many consumer products and biomedical practices. As a result, human exposure to these nanomaterials is highly frequent, becoming an issue of concern to public health. Recently, human salivary leucocytes have been proposed as an adequate non-invasive alternative to peripheral blood leucocytes to evaluate genotoxicity in vitro. The present study focused on proving the suitability of salivary leucocytes as a biomatrix in the comet assay for in vitro nanogenotoxicity studies, by testing some of the metal oxide NPs most frequently present in consumer products, namely, titanium dioxide (TiO₂), zinc oxide (ZnO), and cerium dioxide (CeO₂) NPs. Primary and oxidative DNA damage were evaluated by alkaline and hOGG1-modified comet assay, respectively. Any possible interference of the NPs with the methodological procedure or the hOGG1 activity was addressed before performing genotoxicity evaluation. Results obtained showed an increase of both primary and oxidative damage after NPs treatments. These data support the use of salivary leucocytes as a proper and sensitive biological sample for in vitro nanogenotoxicity studies, and contribute to increase the knowledge on the impact of metal oxide NPs on human health, reinforcing the need for a specific regulation of the nanomaterials use. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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17 pages, 4558 KiB

Open AccessArticle

A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study

by Adrián García-Salvador, Alberto Katsumiti, Elena Rojas, Carol Aristimuño, Mónica Betanzos, Marta Martínez-Moro, Sergio E. Moya and Felipe Goñi-de-Cerio

Nanomaterials 2021, 11(6), 1577; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11061577 - 16 Jun 2021

Cited by 11 | Viewed by 2978

Abstract

Engineered nanomaterials (ENMs) are of significant relevance due to their unique properties, which have been exploited for widespread applications. Cerium oxide nanoparticles (CeO₂-NPs) are one of most exploited ENM in the industry due to their excellent catalytic and multi-enzyme mimetic properties. Thus, the toxicological effects of these ENMs should be further studied. In this study, the acute and subchronic toxicity of CeO₂-NPs were assessed. First, an in vitro multi-dose short-term (24 h) toxicological assessment was performed in three different cell lines: A549 and Calu3 were used to represented lung tissue and 3T3 was used as an interstitial tissue model. After that, a sub-chronic toxicity assessment (90 days) of these NPs was carried out on a realistic and well-established reconstituted primary human airway epithelial model (MucilAir™), cultured at the Air–Liquid Interface (ALI), to study the long-term effects of these particles. Results showed minor toxicity of CeO₂-NPs in acute exposures. However, in subchronic exposures, cytotoxic and inflammatory responses were observed in the human airway epithelial model after 60 days of exposure to CeO₂-NPs. These results suggest that acute toxicity approaches may underestimate the toxicological effect of some ENMs, highlighting the need for subchronic toxicological studies in order to accurately assess the toxicity of ENM and their cumulative effects in organisms. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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24 pages, 1392 KiB

Open AccessArticle

Genotoxicity and Gene Expression in the Rat Lung Tissue following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO₂ NM)

by Fátima Brandão, Carla Costa, Maria João Bessa, Elise Dumortier, Florence Debacq-Chainiaux, Roland Hubaux, Michel Salmon, Julie Laloy, Miruna S. Stan, Anca Hermenean, Sami Gharbia, Anca Dinischiotu, Anne Bannuscher, Bryan Hellack, Andrea Haase, Sónia Fraga and João Paulo Teixeira

Nanomaterials 2021, 11(6), 1502; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11061502 - 07 Jun 2021

Cited by 11 | Viewed by 2839

Abstract

Several reports on amorphous silica nanomaterial (aSiO₂ NM) toxicity have been questioning their safety. Herein, we investigated the in vivo pulmonary toxicity of four variants of aSiO₂ NM: SiO₂_15_Unmod, SiO₂_15_Amino, SiO₂_7 and SiO₂_40. We focused on alterations in lung DNA and protein integrity, and gene expression following single intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO₂_7, using TiO₂_NM105 as a benchmark NM. In the instillation study, a significant but slight increase in oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO₂_15_Amino was observed in the recovery (R) group. Exposure to SiO₂_7 or SiO₂_40 markedly increased oxidative DNA lesions in rat lung cells of the exposure (E) group at every tested dose. This damage seems to be repaired, since no changes compared to controls were observed in the R groups. In STIS, a significant increase in DNA strand breaks of the lung cells exposed to 0.5 mg/m³ of SiO₂_7 or 50 mg/m³ of TiO₂_NM105 was observed in both groups. The detected gene expression changes suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage. Overall, all tested aSiO₂ NM were not associated with marked in vivo toxicity following instillation or STIS. The genotoxicity findings for SiO₂_7 from instillation and STIS are concordant; however, changes in STIS animals were more permanent/difficult to revert. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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12 pages, 2772 KiB

Open AccessArticle

Protective Effect of Lactobacillus rhamnosus GG on TiO₂ Nanoparticles-Induced Oxidative Stress Damage in the Liver of Young Rats

by Penghui Nie, Mengqi Wang, Yu Zhao, Shanji Liu, Ling Chen and Hengyi Xu

Nanomaterials 2021, 11(3), 803; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11030803 - 21 Mar 2021

Cited by 14 | Viewed by 2321

Abstract

The potential toxicity of titanium dioxide nanoparticles (TiO₂ NPs) to mammals has become a widespread concern. Young individuals exposed to TiO₂ NPs have a higher risk than adults. In this study, the protective effects of Lactobacillus rhamnosus GG (LGG) on liver toxicity in young rats induced by TiO₂ NPs were explored. Results show that the four-week-old rats that underwent LGG after the oral intake of TiO₂ NPs could prevent weight loss, reduce hematological indicators (WBC and NEUT) and serum biochemical indicators (AST, ALT, AST/ALT, and ALP). Moreover, it alleviated the pathological damage of the liver (as indicated by the disordered hepatocytes, more eosinophilic, ballooning degeneration, and accompany with blood cells), but it did not reduce the Ti contents in the liver. In addition, RT-qPCR results indicated that LGG restored the expression of anti-oxidative stress-related genes, such as SOD1, SOD2, CAT, HO-1, GSH, GCLC, and GCLM in the liver. In summary, the hepatotoxicity of TiO₂ NPs in young rats is closely related to oxidative stress, and the antioxidant effect of LGG might protect the harmful effects caused by TiO₂ NPs. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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12 pages, 2864 KiB

Open AccessArticle

Investigation of the Immune Modulatory Potential of Zinc Oxide Nanoparticles in Human Lymphocytes

by Helena Moratin, Pascal Ickrath, Agmal Scherzad, Till Jasper Meyer, Sebastian Naczenski, Rudolf Hagen and Stephan Hackenberg

Nanomaterials 2021, 11(3), 629; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11030629 - 03 Mar 2021

Cited by 5 | Viewed by 1935

Abstract

Zinc oxide nanoparticles (ZnO-NP) are commonly used for a variety of applications in everyday life. In addition, due to its versatility, nanotechnology supports promising approaches in the medical sector. NP can act as drug-carriers in the context of targeted chemo- or immunotherapy, and might also exhibit autonomous immune-modulatory characteristics. Knowledge of potential immunosuppressive or stimulating effects of NP is indispensable for the safety of consumers as well as patients. In this study, primary human peripheral blood lymphocytes of 9 donors were treated with different sub-cytotoxic concentrations of ZnO-NP for the duration of 1, 2, or 3 days. Flow cytometry was performed to investigate changes in the activation profile and the proportion of T cell subpopulations. ZnO-NP applied in this study did not induce any significant alterations in the examined markers, indicating their lack of impairment in terms of immune modulation. However, physicochemical characteristics exert a major influence on NP-associated bioactivity. To allow a precise simulation of the complex molecular processes of immune modulation, a physiological model including the different components of an immune response is needed. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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13 pages, 3051 KiB

Open AccessArticle

Interactions of a Water-Soluble Glycofullerene with Glucose Transporter 1. Analysis of the Cellular Effects on a Pancreatic Tumor Model

by Edyta Barańska, Olga Wiecheć-Cudak, Monika Rak, Aleksandra Bienia, Anna Mrozek-Wilczkiewicz, Martyna Krzykawska-Serda and Maciej Serda

Nanomaterials 2021, 11(2), 513; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11020513 - 18 Feb 2021

Cited by 11 | Viewed by 2356

Abstract

In recent years, carbon nanomaterials have been intensively investigated for their possible applications in biomedical studies, especially as drug delivery vehicles. Several surface modifications can modulate the unique molecular structure of [60]fullerene derivatives, as well as their physicochemical properties. For this reason, covalent modifications that would enable a greater water solubilization of the fullerene buckyball have been rapidly investigated. The most exciting applications of fullerene nanomaterials are as drug delivery vectors, photosensitizers in photodynamic therapy (PDT), astransfection or MRI contrast agents, antimicrobials and antioxidants. From these perspectives, the glucose derivatives of [60]fullerene seem to be an interesting carbon nanomaterial for biological studies. It is well-known that cancer cells are characterized by an increased glucose uptake and it has also been previously reported that the glucose transporters (GLUTs) are overexpressed in several types of cancers, which make them attractive molecular targets for many drugs. This study explored the use of a highly water-soluble glycofullerene (called Sweet-C₆₀) in pancreatic cancer studies. Here, we describe the PANC-1 cell proliferation, migration, metabolic activity and glycolysis rate after incubations with different concentrations of Sweet-C₆₀. The final results did not show any influence of the Sweet-C₆₀ on various cancer cellular events and glycolysis, suggesting that synthesized glycofullerene is a promising drug delivery vehicle for treating pancreatic cancer. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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16 pages, 7105 KiB

Open AccessArticle

New Insights into the Cell Death Signaling Pathways Triggered by Long-Term Exposure to Silicon-Based Quantum Dots in Human Lung Fibroblasts

by Miruna S. Stan, Smaranda Badea, Anca Hermenean, Hildegard Herman, Bogdan Trica, Beatrice G. Sbarcea and Anca Dinischiotu

Nanomaterials 2021, 11(2), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/nano11020323 - 27 Jan 2021

Cited by 9 | Viewed by 1824

Abstract

This report is the first research study that aims to explore the molecular mechanisms involved in the in vitro pulmonary cytotoxicity triggered by long-term exposure to silicon-based quantum dots (QDs). Human lung fibroblasts (MRC-5 cell line) were exposed to 5 µg/mL silicon-based QDs for 5 weeks and the concentration was increased up to 40 µg/mL QDs during the next 4 weeks. Cell viability and population doubling level were calculated based on Trypan blue staining. The expression levels of proteins were established by Western blotting and the telomeres’ length was determined through Southern blotting. Prolonged exposure of lung fibroblasts to QDs reduced the cell viability by 10% compared to untreated cells. The level of p53 and apoptosis-inducing factor (AIF) expression increased during the exposure, the peak intensity being registered after the seventh week. The expressions of autophagy-related proteins, Beclin-1 and LC-3, were higher compared to untreated cells. Regarding the protein expression of Nrf-2, a progressive decrease was noticed, suggesting the downregulation of a cytoprotective response to oxidative stress. In contrast, the heat shock proteins’ (HSPs) expression was increased or maintained near the control level during QDs exposure in order to promote cell survival. Furthermore, the telomeres’ length was not reduced during this exposure, indicating that QDs did not induce cellular senescence. In conclusion, our study shows that silicon-based QDs triggered the activation of apoptotic and autophagy pathways and downregulation of survival signaling molecules as an adaptive response to cellular stress which was not associated with telomeres shortening. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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28 pages, 6066 KiB

Open AccessArticle

Developmental Neurotoxicity Screening for Nanoparticles Using Neuron-Like Cells of Human Umbilical Cord Mesenchymal Stem Cells: Example with Magnetite Nanoparticles

by Teresa Coccini, Patrizia Pignatti, Arsenio Spinillo and Uliana De Simone

Nanomaterials 2020, 10(8), 1607; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10081607 - 15 Aug 2020

Cited by 12 | Viewed by 3061

Abstract

Metallic nanoparticles (NPs), as iron oxide NPs, accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Human stem cell-derived in vitro models may provide more realistic platforms to study NPs effects on neural cells, and to obtain relevant information on the potential for early or late DNT effects in humans. Primary neuronal-like cells (hNLCs) were generated from mesenchymal stem cells derived from human umbilical cord lining and the effects caused by magnetite (Fe₃O₄NPs, 1–50 μg/mL) evaluated. Neuronal differentiation process was divided into stages: undifferentiated, early, mid- and fully-differentiated (from day-2 to 8 of induction) based on different neuronal markers and morphological changes over time. Reduction in neuronal differentiation induction after NP exposure was observed associated with NP uptake: β-tubulin III (β-Tub III), microtubule-associated protein 2 (MAP-2), enolase (NSE) and nestin were downregulated (10–40%), starting from 25 μg/mL at the early stage. Effects were exacerbated at higher concentrations and persisted up to 8 days without cell morphology alterations. Adenosine triphosphate (ATP) and caspase-3/7 activity data indicated Fe₃O₄NPs-induced cell mortality in a concentration-dependent manner and increases of apoptosis: effects appeared early (from day-3), started at low concentrations (≥5 μg/mL) and persisted. This new human cell-based model allows different stages of hNLCs to be cultured, exposed to NPs/chemicals, and analyzed for different endpoints at early or later developmental stage. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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25 pages, 10065 KiB

Open AccessArticle

Effects of Functionalized Fullerenes on ROS Homeostasis Determine Their Cytoprotective or Cytotoxic Properties

by Svetlana V. Kostyuk, Elena V. Proskurnina, Ekaterina A. Savinova, Elizaveta S. Ershova, Olga A. Kraevaya, Larisa V. Kameneva, Pavel E. Umryukhin, Olga A. Dolgikh, Sergey I. Kutsev, Pavel A. Troshin and Natalia N. Veiko

Nanomaterials 2020, 10(7), 1405; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10071405 - 19 Jul 2020

Cited by 7 | Viewed by 2537

Abstract

Background: Functionalized fullerenes (FF) can be considered regulators of intracellular reactive oxygen species (ROS) homeostasis; their direct oxidative damage—as well as regulation of oxidant enzymes and signaling pathways—should be considered. Methods: Uptake of two water-soluble functionalized C₇₀ fullerenes with different types of aromatic addends (ethylphenylmalonate and thienylacetate) in human fetal lung fibroblasts, intracellular ROS visualization, superoxide scavenging potential, NOX4 expression, NRF2 expression, oxidative DNA damage, repair genes, cell proliferation and cell cycle were studied. Results & conclusion: The intracellular effects of ethylphenylmalonate C₇₀ derivative (FF1) can be explained in terms of upregulated NOX4 activity. The intracellular effects of thienylacetate C₇₀ derivative (FF2) can be probably resulted from its superoxide scavenging potential and inhibition of lipid peroxidation. FF1 can be considered a NOX4 upregulator and potential cytotoxicant and FF2, as a superoxide scavenger and a potential cytoprotector. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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Review

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56 pages, 6563 KiB

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Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

by Laura Rueda-Gensini, Javier Cifuentes, Maria Claudia Castellanos, Paola Ruiz Puentes, Julian A. Serna, Carolina Muñoz-Camargo and Juan C. Cruz

Nanomaterials 2020, 10(9), 1816; https://0-doi-org.brum.beds.ac.uk/10.3390/nano10091816 - 11 Sep 2020

Cited by 41 | Viewed by 8912

Abstract

Iron oxide nanoparticles (IONs) have been widely explored for biomedical applications due to their high biocompatibility, surface-coating versatility, and superparamagnetic properties. Upon exposure to an external magnetic field, IONs can be precisely directed to a region of interest and serve as exceptional delivery vehicles and cellular markers. However, the design of nanocarriers that achieve an efficient endocytic uptake, escape lysosomal degradation, and perform precise intracellular functions is still a challenge for their application in translational medicine. This review highlights several aspects that mediate the activation of the endosomal pathways, as well as the different properties that govern endosomal escape and nuclear transfection of magnetic IONs. In particular, we review a variety of ION surface modification alternatives that have emerged for facilitating their endocytic uptake and their timely escape from endosomes, with special emphasis on how these can be manipulated for the rational design of cell-penetrating vehicles. Moreover, additional modifications for enhancing nuclear transfection are also included in the design of therapeutic vehicles that must overcome this barrier. Understanding these mechanisms opens new perspectives in the strategic development of vehicles for cell tracking, cell imaging and the targeted intracellular delivery of drugs and gene therapy sequences and vectors. Full article

(This article belongs to the Special Issue Cytotoxicity and Genotoxicity of Nanomaterials)

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