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Mechanisms of Cellular Toxicity of Nanoparticles

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 October 2020) | Viewed by 23407

Special Issue Editor

Institute of Experimental Medicine of the Academy of Sciences of the Czech Republic, Prague, Czech Republic
Interests: nanotoxicology; oxidative stress; gene expression modulation; epigenetics; in vitro systems; human studies; 3D models; air pollution; engine emissions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The application of nanomaterials (NM) in everyday life is constantly increasing. NM are used, e.g., in cosmetics, medicine, the food industry, electronics or chemistry. As a result, humans are exposed to various types and mixtures of NM that may impact health and contribute to development of numerous diseases. To reveal biological consequences of NM exposure, the toxicity of NM and mechanisms of induction of their negative effects should be investigated. This is a major aim of the Special Issue. Manuscripts to be considered should focus on mechanisms of toxicity of diverse NM, preferable those commonly used, in relevant cell lines, 3D models or in experimental animals. Studies focusing on human exposure to NM are also welcome. The authors should avoid presentation of basic toxicity markers (e.g., cytotoxicity), but more complex approaches including genomics and proteomics are rather encouraged. Ideally, a battery of toxicity markers should be applied to reveal interactions between NM and the test system and biochemical pathways induced by the exposure.

Dr. Pavel Rossner
Guest Editor

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Keywords

  • nanomaterials
  • cell lines
  • humans
  • toxicity
  • mechanisms

Published Papers (7 papers)

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Research

20 pages, 6902 KiB  
Article
Early Postnatal Exposure to a Low Dose of Nanoparticulate Silver Induces Alterations in Glutamate Transporters in Brain of Immature Rats
by Beata Dąbrowska-Bouta, Grzegorz Sulkowski, Mikołaj Sałek, Magdalena Gewartowska, Marta Sidoryk-Węgrzynowicz and Lidia Strużyńska
Int. J. Mol. Sci. 2020, 21(23), 8977; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238977 - 26 Nov 2020
Cited by 7 | Viewed by 1689
Abstract
Due to strong antimicrobial properties, silver nanoparticles (AgNPs) are used in a wide range of medical and consumer products, including those dedicated for infants and children. While AgNPs are known to exert neurotoxic effects, current knowledge concerning their impact on the developing brain [...] Read more.
Due to strong antimicrobial properties, silver nanoparticles (AgNPs) are used in a wide range of medical and consumer products, including those dedicated for infants and children. While AgNPs are known to exert neurotoxic effects, current knowledge concerning their impact on the developing brain is scarce. During investigations of mechanisms of neurotoxicity in immature rats, we studied the influence of AgNPs on glutamate transporter systems which are involved in regulation of extracellular concentration of glutamate, an excitotoxic amino acid, and compared it with positive control—Ag citrate. We identified significant deposition of AgNPs in brain tissue of exposed rats over the post-exposure time. Ultrastructural alterations in endoplasmic reticulum (ER) and Golgi complexes were observed in neurons of AgNP-exposed rats, which are characteristics of ER stress. These changes presumably underlie substantial long-lasting downregulation of neuronal glutamate transporter EAAC1, which was noted in AgNP-exposed rats. Conversely, the expression of astroglial glutamate transporters GLT-1 and GLAST was not affected by exposure to AgNPs, but the activity of the transporters was diminished. These results indicate that even low doses of AgNPs administered during an early stage of life create a substantial risk for health of immature organisms. Hence, the safety of AgNP-containing products for infants and children should be carefully considered. Full article
(This article belongs to the Special Issue Mechanisms of Cellular Toxicity of Nanoparticles)
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16 pages, 5041 KiB  
Article
Assessment of Polyethylene Glycol-Coated Gold Nanoparticle Toxicity and Inflammation In Vivo Using NF-κB Reporter Mice
by Tzu-Yin Chen, Mei-Ru Chen, Shan-Wen Liu, Jin-Yan Lin, Ya-Ting Yang, Hsin-Ying Huang, Jen-Kun Chen, Chung-Shi Yang and Kurt Ming-Chao Lin
Int. J. Mol. Sci. 2020, 21(21), 8158; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218158 - 31 Oct 2020
Cited by 15 | Viewed by 2778
Abstract
Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, [...] Read more.
Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-κB transgenic reporter mice following intravenous injection of PEG-coated AuNPs. The results of different doses (1 and 4 μg AuNPs per gram of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-κB reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathological abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver; thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health. Full article
(This article belongs to the Special Issue Mechanisms of Cellular Toxicity of Nanoparticles)
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23 pages, 2885 KiB  
Article
Toxicity of TiO2 Nanoparticles: Validation of Alternative Models
by Mélanie M. Leroux, Zahra Doumandji, Laetitia Chézeau, Laurent Gaté, Sara Nahle, Romain Hocquel, Vadim Zhernovkov, Sylvie Migot, Jafar Ghanbaja, Céline Bonnet, Raphaël Schneider, Bertrand H. Rihn, Luc Ferrari and Olivier Joubert
Int. J. Mol. Sci. 2020, 21(14), 4855; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144855 - 09 Jul 2020
Cited by 10 | Viewed by 3736
Abstract
There are many studies concerning titanium dioxide (TiO2) nanoparticles (NP) toxicity. Nevertheless, there are few publications comparing in vitro and in vivo exposure, and even less comparing air–liquid interface exposure (ALI) with other in vitro and in vivo exposures. The identification [...] Read more.
There are many studies concerning titanium dioxide (TiO2) nanoparticles (NP) toxicity. Nevertheless, there are few publications comparing in vitro and in vivo exposure, and even less comparing air–liquid interface exposure (ALI) with other in vitro and in vivo exposures. The identification and validation of common markers under different exposure conditions are relevant for the development of smart and quick nanotoxicity tests. In this work, cell viability was assessed in vitro by WST-1 and LDH assays after the exposure of NR8383 cells to TiO2 NP sample. To evaluate in vitro gene expression profile, NR8383 cells were exposed to TiO2 NP during 4 h at 3 cm2 of TiO2 NP/cm2 of cells or 19 μg/mL, in two settings—submerged cultures and ALI. For the in vivo study, Fischer 344 rats were exposed by inhalation to a nanostructured aerosol at a concentration of 10 mg/m3, 6 h/day, 5 days/week for 4 weeks. This was followed immediately by gene expression analysis. The results showed a low cytotoxic potential of TiO2 NP on NR8383 cells. Despite the absence of toxicity at the doses studied, the different exposures to TiO2 NP induce 18 common differentially expressed genes (DEG) which are involved in mitosis regulation, cell proliferation and apoptosis and inflammation transport of membrane proteins. Among these genes, we noticed the upregulation of Ccl4, Osm, Ccl7 and Bcl3 genes which could be suggested as early response biomarkers after exposure to TiO2 NP. On the other hand, the comparison of the three models helped us to validate the alternative ones, namely submerged and ALI approaches. Full article
(This article belongs to the Special Issue Mechanisms of Cellular Toxicity of Nanoparticles)
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23 pages, 5192 KiB  
Article
The Differential Effect of Carbon Dots on Gene Expression and DNA Methylation of Human Embryonic Lung Fibroblasts as a Function of Surface Charge and Dose
by Michal Sima, Kristyna Vrbova, Tana Zavodna, Katerina Honkova, Irena Chvojkova, Antonin Ambroz, Jiri Klema, Andrea Rossnerova, Katerina Polakova, Tomas Malina, Jan Belza, Jan Topinka and Pavel Rossner, Jr.
Int. J. Mol. Sci. 2020, 21(13), 4763; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134763 - 04 Jul 2020
Cited by 18 | Viewed by 2711
Abstract
This study presents a toxicological evaluation of two types of carbon dots (CD), similar in size (<10 nm) but differing in surface charge. Whole-genome mRNA and miRNA expression (RNAseq), as well as gene-specific DNA methylation changes, were analyzed in human embryonic lung fibroblasts [...] Read more.
This study presents a toxicological evaluation of two types of carbon dots (CD), similar in size (<10 nm) but differing in surface charge. Whole-genome mRNA and miRNA expression (RNAseq), as well as gene-specific DNA methylation changes, were analyzed in human embryonic lung fibroblasts (HEL 12469) after 4 h and 24 h exposure to concentrations of 10 and 50 µg/mL (for positive charged CD; pCD) or 10 and 100 µg/mL (for negative charged CD, nCD). The results showed a distinct response for the tested nanomaterials (NMs). The exposure to pCD induced the expression of a substantially lower number of mRNAs than those to nCD, with few commonly differentially expressed genes between the two CDs. For both CDs, the number of deregulated mRNAs increased with the dose and exposure time. The pathway analysis revealed a deregulation of processes associated with immune response, tumorigenesis and cell cycle regulation, after exposure to pCD. For nCD treatment, pathways relating to cell proliferation, apoptosis, oxidative stress, gene expression, and cycle regulation were detected. The expression of miRNAs followed a similar pattern: more pronounced changes after nCD exposure and few commonly differentially expressed miRNAs between the two CDs. For both CDs the pathway analysis based on miRNA-mRNA interactions, showed a deregulation of cancer-related pathways, immune processes and processes involved in extracellular matrix interactions. DNA methylation was not affected by exposure to any of the two CDs. In summary, although the tested CDs induced distinct responses on the level of mRNA and miRNA expression, pathway analyses revealed a potential common biological impact of both NMs independent of their surface charge. Full article
(This article belongs to the Special Issue Mechanisms of Cellular Toxicity of Nanoparticles)
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20 pages, 4842 KiB  
Article
DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles
by Andrea Rossnerova, Katerina Honkova, Daniela Pelclova, Vladimir Zdimal, Jaroslav A. Hubacek, Irena Chvojkova, Kristyna Vrbova, Pavel Rossner, Jr., Jan Topinka, Stepanka Vlckova, Zdenka Fenclova, Lucie Lischkova, Pavlina Klusackova, Jaroslav Schwarz, Jakub Ondracek, Lucie Ondrackova, Martin Kostejn, Jiri Klema and Stepanka Dvorackova
Int. J. Mol. Sci. 2020, 21(7), 2420; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072420 - 31 Mar 2020
Cited by 28 | Viewed by 2911
Abstract
The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA [...] Read more.
The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA alterations are still rare. Furthermore, there are virtually no epigenetic data available. In this study, we investigated global and gene-specific DNA methylation profiles in a group of 20 long-term (mean 14.5 years) exposed, nanocomposite, research workers and in 20 controls. Both groups were sampled twice/day (pre-shift and post-shift) in September 2018. We applied Infinium Methylation Assay, using the Infinium MethylationEPIC BeadChips with more than 850,000 CpG loci, for identification of the DNA methylation pattern in the studied groups. Aerosol exposure monitoring, including two nanosized fractions, was also performed as proof of acute NP exposure. The obtained array data showed significant differences in methylation between the exposed and control groups related to long-term exposure, specifically 341 CpG loci were hypomethylated and 364 hypermethylated. The most significant CpG differences were mainly detected in genes involved in lipid metabolism, the immune system, lung functions, signaling pathways, cancer development and xenobiotic detoxification. In contrast, short-term acute NP exposure was not accompanied by DNA methylation changes. In summary, long-term (years) exposure to NP is associated with DNA epigenetic alterations. Full article
(This article belongs to the Special Issue Mechanisms of Cellular Toxicity of Nanoparticles)
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14 pages, 5291 KiB  
Article
Green Synthesis of Silver Nanoparticles Using Pseudoduganella eburnea MAHUQ-39 and Their Antimicrobial Mechanisms Investigation against Drug Resistant Human Pathogens
by Md. Amdadul Huq
Int. J. Mol. Sci. 2020, 21(4), 1510; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041510 - 22 Feb 2020
Cited by 131 | Viewed by 6246
Abstract
Silver nanoparticles (AgNPs) have shown great promise in biomedical applications. The exact mechanism and mode of action of AgNPs regarding antimicrobial activity are still not well known. Moreover, synthesis of nanoparticles by physical and chemical methods is expensive and not ecofriendly. This study [...] Read more.
Silver nanoparticles (AgNPs) have shown great promise in biomedical applications. The exact mechanism and mode of action of AgNPs regarding antimicrobial activity are still not well known. Moreover, synthesis of nanoparticles by physical and chemical methods is expensive and not ecofriendly. This study highlights the green, rapid, facile, cost-effective and ecofriendly synthesis of AgNPs using Pseudoduganella eburnea MAHUQ-39 and also investigates their antibacterial mechanisms. The transmission electron microscopy (TEM) image revealed a spherical shape of the AgNPs. The size of the synthesized AgNPs was 8 to 24 nm. The elemental mapping and selected area electron diffraction (SAED) and X-ray diffraction (XRD) patterns revealed the crystalline structure of AgNPs. Fourier-transform infrared spectroscopy (FTIR) analysis identified the functional groups that are involved in the reduction of silver ion to AgNPs. The green synthesized AgNPs exhibited strong antimicrobial activity against multidrug-resistant pathogenic microbes. Minimal inhibitory concentrations (MICs) of Staphylococcus aureus and Pseudomonas aeruginosa were 100 μg/mL and 6.25 μg/mL, respectively, and the minimum bactericidal concentrations (MBCs) of S. aureus and P. aeruginosa were 200 μg/mL and 50 μg/mL, respectively. Our data demonstrated that synthesized AgNPs created structural changes of cells and destroyed the membrane integrity of strains S. aureus and P. aeruginosa. Therefore, AgNPs synthesized by strain MAHUQ-39 can be used as a powerful antimicrobial agent for various therapeutic applications. Full article
(This article belongs to the Special Issue Mechanisms of Cellular Toxicity of Nanoparticles)
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21 pages, 4157 KiB  
Article
Effects of Iron Oxide Nanoparticles (γ-Fe2O3) on Liver, Lung and Brain Proteomes following Sub-Acute Intranasal Exposure: A New Toxicological Assessment in Rat Model Using iTRAQ-Based Quantitative Proteomics
by Dalel Askri, Valérie Cunin, Souhir Ouni, David Béal, Walid Rachidi, Mohsen Sakly, Salem Amara, Sylvia G. Lehmann and Michel Sève
Int. J. Mol. Sci. 2019, 20(20), 5186; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20205186 - 19 Oct 2019
Cited by 10 | Viewed by 2887
Abstract
Iron Oxide Nanoparticles (IONPs) present unique properties making them one of the most used NPs in the biomedical field. Nevertheless, for many years, growing production and use of IONPs are associated with risks that can affect human and the environment. Thus, it is [...] Read more.
Iron Oxide Nanoparticles (IONPs) present unique properties making them one of the most used NPs in the biomedical field. Nevertheless, for many years, growing production and use of IONPs are associated with risks that can affect human and the environment. Thus, it is essential to study the effects of these nanoparticles to better understand their mechanism of action and the molecular perturbations induced in the organism. In the present study, we investigated the toxicological effects of IONPs (γ-Fe2O3) on liver, lung and brain proteomes in Wistar rats. Exposed rats received IONP solution during 7 consecutive days by intranasal instillation at a dose of 10 mg/kg body weight. An iTRAQ-based quantitative proteomics was used to study proteomic variations at the level of the three organs. Using this proteomic approach, we identified 1565; 1135 and 1161 proteins respectively in the brain, liver and lung. Amon them, we quantified 1541; 1125 and 1128 proteins respectively in the brain, liver and lung. Several proteins were dysregulated comparing treated samples to controls, particularly, proteins involved in cytoskeleton remodeling, cellular metabolism, immune system stimulation, inflammation process, response to oxidative stress, angiogenesis, and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Mechanisms of Cellular Toxicity of Nanoparticles)
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