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Nanomaterials
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Advances in Toxicity of Nanoparticles
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Advances in Toxicity of Nanoparticles

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

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 22860

Special Issue Editor

Dr. Chiara Uboldi

E-Mail Website
Guest Editor
Mediterranean Institute of Marine and Terrestrial Biodiversity and Ecology (IMBE), Faculty of Medical and Paramedical Sciences, Aix-Marseille University, 27 boulevard Jean Moulin, 13005 Marseille, France
Interests: nanoparticles; cytotoxicity; DNA damage; oxidative stress; internalization; risk assessment

Special Issue Information

Dear Colleagues,

This Special Issue is open to valuable contributions presenting advances on the elucidation of the potential toxic effects of nanoparticles. For years, humans have been exposed—intentionally or unintentionally—to a broad range of nanoparticle-containing products. Many efforts have been made to identify the risks to which we are exposed, but concerns are still growing when it comes to dealing with nanoparticles. Moreover, nanoparticles can also affect the environment and induce effects either on aquatic or terrestrial species or on humans.

In this Special Issue, we welcome papers reporting on: i) nanoparticles’ physicochemical modifications occurring throughout their lifecycle and exerting toxic responses; ii) in vitro, ex vivo, and in vivo methods to test nanoparticles toxicity; iii) improved protocols or new methods to test nanoparticles’ cytotoxicity, mutagenicity, DNA damage, oxidative stress, inflammation, and intracellular localization/quantification; and iv) mechanistic studies on the toxicological mode of action of nanoparticles.

Dr. Chiara Uboldi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nanomaterials is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 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

  • nanoparticles
  • physicochemical properties
  • cytotoxicity
  • DNA damage
  • oxidative stress
  • internalization
  • risk assessment
  • in vitro, ex vivo, and in vivo methods

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Published Papers (8 papers)

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Research

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13 pages, 3816 KiB  
Article
In Vitro and In Vivo Biocompatibility of Boron/Nitrogen Co-Doped Carbon Nano-Onions
by Marta d’Amora, Adalberto Camisasca, Raul Arenal and Silvia Giordani
Nanomaterials 2021, 11(11), 3017; https://doi.org/10.3390/nano11113017 - 10 Nov 2021
Cited by 5 | Viewed by 2668
Abstract
Boron/nitrogen, co-doped, carbon nano-onions (BN-CNOs) have recently shown great promise as catalysts for the oxygen reduction reaction, due to the improved electronic properties imparted by the dopant atoms; however, the interactions of BN-CNOs with biological systems have not yet been explored. In this [...] Read more.
Boron/nitrogen, co-doped, carbon nano-onions (BN-CNOs) have recently shown great promise as catalysts for the oxygen reduction reaction, due to the improved electronic properties imparted by the dopant atoms; however, the interactions of BN-CNOs with biological systems have not yet been explored. In this study, we examined the toxicological profiles of BN-CNOs and oxidized BN-CNOs (oxi-BN-CNOs) in vitro in both healthy and cancer cell lines, as well as on the embryonic stages of zebrafish (Danio rerio) in vivo. The cell viabilities of both cell lines cells were not affected after treatment with different concentrations of both doped CNO derivatives. On the other hand, the analysis of BN-CNOs and oxidized BN-CNO interactions with zebrafish embryos did not report any kind of perturbations, in agreement with the in vitro results. Our results show that both doped CNO derivatives possess a high biocompatibility and biosafety in cells and more complex systems. Full article
(This article belongs to the Special Issue Advances in Toxicity of Nanoparticles)
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20 pages, 3969 KiB  
Article
Ingested Engineered Nanomaterials Affect the Expression of Mucin Genes—An In Vitro-In Vivo Comparison
by Gerrit Bredeck, Angela A. M. Kämpfer, Adriana Sofranko, Tina Wahle, Veronika Büttner, Catrin Albrecht and Roel P. F. Schins
Nanomaterials 2021, 11(10), 2621; https://doi.org/10.3390/nano11102621 - 6 Oct 2021
Cited by 4 | Viewed by 2566
Abstract
The increasing use of engineered nanomaterials (ENM) in food has fueled the development of intestinal in vitro models for toxicity testing. However, ENM effects on intestinal mucus have barely been addressed, although its crucial role for intestinal health is evident. We investigated the [...] Read more.
The increasing use of engineered nanomaterials (ENM) in food has fueled the development of intestinal in vitro models for toxicity testing. However, ENM effects on intestinal mucus have barely been addressed, although its crucial role for intestinal health is evident. We investigated the effects of ENM on mucin expression and aimed to evaluate the suitability of four in vitro models of increasing complexity compared to a mouse model exposed through feed pellets. We assessed the gene expression of the mucins MUC1, MUC2, MUC5AC, MUC13 and MUC20 and the chemokine interleukin-8 in pre-confluent and confluent HT29-MTX-E12 cells, in stable and inflamed triple cultures of Caco-2, HT29-MTX-E12 and THP-1 cells, and in the ileum of mice following exposure to TiO2, Ag, CeO2 or SiO2. All ENM had shared and specific effects. CeO2 downregulated MUC1 in confluent E12 cells and in mice. Ag induced downregulation of Muc2 in mice. Overall, the in vivo data were consistent with the findings in the stable triple cultures and the confluent HT29-MTX-E12 cells but not in pre-confluent cells, indicating the higher relevance of advanced models for hazard assessment. The effects on MUC1 and MUC2 suggest that specific ENM may lead to an elevated susceptibility towards intestinal infections and inflammations. Full article
(This article belongs to the Special Issue Advances in Toxicity of Nanoparticles)
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10 pages, 4103 KiB  
Article
Combination of Mussel Inspired Method and “Thiol-Michael” Click Reaction for Biocompatible Alginate-Modified Carbon Nanotubes
by Haiyan Yao, Mingzhi Zhu, Pei Wang, Yuangang Liu and Junchao Wei
Nanomaterials 2021, 11(9), 2191; https://doi.org/10.3390/nano11092191 - 26 Aug 2021
Cited by 5 | Viewed by 2381
Abstract
Carbon nanotubes (CNTs) have attracted great interest in biomedical fields. However, the potential toxicity and poor dispersion of CNTs have greatly limited its application. In this work, a mussel-inspired method combined with the “thiol-Michael” click reaction was used to modify the surface of [...] Read more.
Carbon nanotubes (CNTs) have attracted great interest in biomedical fields. However, the potential toxicity and poor dispersion of CNTs have greatly limited its application. In this work, a mussel-inspired method combined with the “thiol-Michael” click reaction was used to modify the surface of CNT and improve its properties. Firstly, a CNT was treated with dopamine, and then alginate grafted with L-cysteine was anchored onto the surface of CNT via click reaction, which realized the long-time dispersion of CNT in water. Furthermore, the in vitro test also demonstrated that the alginate may improve the biocompatibility of CNT, and thus may broaden the application of CNT in the biomedical field. Full article
(This article belongs to the Special Issue Advances in Toxicity of Nanoparticles)
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13 pages, 3462 KiB  
Article
In Vitro Co-Exposure to CeO2 Nanomaterials from Diesel Engine Exhaust and Benzo(a)Pyrene Induces Additive DNA Damage in Sperm and Cumulus Cells but Not in Oocytes
by Martina Cotena, Mélanie Auffan, Virginie Tassistro, Noémie Resseguier, Jérôme Rose and Jeanne Perrin
Nanomaterials 2021, 11(2), 478; https://doi.org/10.3390/nano11020478 - 13 Feb 2021
Cited by 6 | Viewed by 2479
Abstract
Benzo(a)pyrene (BaP) is a recognized reprotoxic compound and the most widely investigated polycyclic aromatic hydrocarbon in ambient air; it is widespread by the incomplete combustion of fossil fuels along with cerium dioxide nanomaterials (CeO2 NMs), which are used in nano-based [...] Read more.
Benzo(a)pyrene (BaP) is a recognized reprotoxic compound and the most widely investigated polycyclic aromatic hydrocarbon in ambient air; it is widespread by the incomplete combustion of fossil fuels along with cerium dioxide nanomaterials (CeO2 NMs), which are used in nano-based diesel additives to decrease the emission of toxic compounds and to increase fuel economy. The toxicity of CeO2 NMs on reproductive organs and cells has also been shown. However, the effect of the combined interactions of BaP and CeO2 NMs on reproduction has not been investigated. Herein, human and rat gametes were exposed in vitro to combusted CeO2 NMs or BaP or CeO2 NMs and BaP in combination. CeO2 NMs were burned at 850 °C prior to mimicking their release after combustion in a diesel engine. We demonstrated significantly higher amounts of DNA damage after exposure to combusted CeO2 NMs (1 µg·L−1) or BaP (1.13 µmol·L−1) in all cell types considered compared to unexposed cells. Co-exposure to the CeO2 NMs-BaP mixture induced additive DNA damage in sperm and cumulus cells, whereas no additive effect was observed in rat oocytes. This result could be related to the structural protection of the oocyte by cumulus cells and to the oocyte’s efficient system to repair DNA damage compared to that of cumulus and sperm cells. Full article
(This article belongs to the Special Issue Advances in Toxicity of Nanoparticles)
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17 pages, 4854 KiB  
Article
Assessment of the Influence of Crystalline Form on Cyto-Genotoxic and Inflammatory Effects Induced by TiO2 Nanoparticles on Human Bronchial and Alveolar Cells
by Anna Maria Fresegna, Cinzia Lucia Ursini, Aureliano Ciervo, Raffaele Maiello, Stefano Casciardi, Sergio Iavicoli and Delia Cavallo
Nanomaterials 2021, 11(1), 253; https://doi.org/10.3390/nano11010253 - 19 Jan 2021
Cited by 17 | Viewed by 2909
Abstract
Titanium dioxide nanoparticles (TiO2NPs) are increasingly used in consumer products, industrial and medical applications, raising concerns on their potential toxicity. The available in vitro and in vivo studies on these NPs show controversial results. Crystalline structure is the physicochemical characteristic that [...] Read more.
Titanium dioxide nanoparticles (TiO2NPs) are increasingly used in consumer products, industrial and medical applications, raising concerns on their potential toxicity. The available in vitro and in vivo studies on these NPs show controversial results. Crystalline structure is the physicochemical characteristic that seems to influence mainly TiO2NPs toxicity, so its effect needs to be further studied. We aimed to study whether and how crystalline form influences potential cyto-genotoxic and inflammatory effects induced by two commercial TiO2NPs (TiO2-A, mainly anatase; TiO2-B, mainly rutile) in human alveolar A549 and bronchial BEAS-2B cells exposed to 1–40 µg/mL. Cell viability (WST-1), membrane damage (LDH release), IL-6, IL-8 and TNF-α release (ELISA) and direct/oxidative DNA damage (fpg-comet assay) were evaluated. Physicochemical characterization included analysis of crystalline form (TEM and XRD), specific surface area (BET), agglomeration (DLS) and Z-potential (ELS). Our results show that TiO2-A NPs induce in BEAS-2B cytotoxicity and a slight inflammation and in A549 slight oxidative effects, whereas TiO2-B NPs induce genotoxic/oxidative effects in both cell lines, revealing different toxicity mechanisms for the two tested NPs. In conclusion, our study confirms the influence of crystalline form on cellular response, also demonstrating the suitability of our in vitro model to screen early TiO2NPs effects. Full article
(This article belongs to the Special Issue Advances in Toxicity of Nanoparticles)
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14 pages, 1070 KiB  
Article
CeO2 Nanomaterials from Diesel Engine Exhaust Induce DNA Damage and Oxidative Stress in Human and Rat Sperm In Vitro
by Martina Cotena, Mélanie Auffan, Stéphane Robert, Virginie Tassistro, Noémie Resseguier, Jérôme Rose and Jeanne Perrin
Nanomaterials 2020, 10(12), 2327; https://doi.org/10.3390/nano10122327 - 24 Nov 2020
Cited by 6 | Viewed by 2682
Abstract
Cerium dioxide nanomaterials (CeO2 NMs) are widely used in nano-based diesel additives to decrease the emission of toxic compounds, but they have been shown to increase the emission of ultrafine particles as well as the amount of released Ce. The Organization for [...] Read more.
Cerium dioxide nanomaterials (CeO2 NMs) are widely used in nano-based diesel additives to decrease the emission of toxic compounds, but they have been shown to increase the emission of ultrafine particles as well as the amount of released Ce. The Organization for Economic Cooperation and Development included CeO2 NMs in the priority list of nanomaterials that require urgent evaluation, and the potential hazard of aged CeO2 NM exposure remains unexplored. Herein, human and rat sperm cells were exposed in vitro to a CeO2 NM-based diesel additive (called EnviroxTM), burned at 850 °C to mimic its release after combustion in a diesel engine. We demonstrated significant DNA damage after in vitro exposure to the lowest tested concentration (1 µg·L−1) using the alkaline comet assay (ACA). We also showed a significant increase in oxidative stress in human sperm after in vitro exposure to 1 µg·L−1 aged CeO2 NMs evaluated by the H2DCF-DA probe. Electron microscopy showed no internalization of aged CeO2 NMs in human sperm but an affinity for the head plasma membrane. The results obtained in this study provide some insight on the complex cellular mechanisms by which aged CeO2 NMs could exert in vitro biological effects on human spermatozoa and generate ROS. Full article
(This article belongs to the Special Issue Advances in Toxicity of Nanoparticles)
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17 pages, 4860 KiB  
Article
Nickel Nanoparticles Induce the Synthesis of a Tumor-Related Polypeptide in Human Epidermal Keratinocytes
by Javier Jiménez-Lamana, Simon Godin, Gerard Aragonès, Cinta Bladé, Joanna Szpunar and Ryszard Łobinski
Nanomaterials 2020, 10(5), 992; https://doi.org/10.3390/nano10050992 - 21 May 2020
Cited by 8 | Viewed by 3021
Abstract
Although nickel allergy and carcinogenicity are well known, their molecular mechanisms are still uncertain, thus demanding studies at the molecular level. The nickel carcinogenicity is known to be dependent on the chemical form of nickel, since only certain nickel compounds can enter the [...] Read more.
Although nickel allergy and carcinogenicity are well known, their molecular mechanisms are still uncertain, thus demanding studies at the molecular level. The nickel carcinogenicity is known to be dependent on the chemical form of nickel, since only certain nickel compounds can enter the cell. This study investigates, for the first time, the cytotoxicity, cellular uptake, and molecular targets of nickel nanoparticles (NiNPs) in human skin cells in comparison with other chemical forms of nickel. The dose-response curve that was obtained for NiNPs in the cytotoxicity assays showed a linear behavior typical of genotoxic carcinogens. The exposure of keratinocytes to NiNPs leads to the release of Ni2+ ions and its accumulation in the cytosol. A 6 kDa nickel-binding molecule was found to be synthesized by cells exposed to NiNPs at a dose corresponding to medium mortality. This molecule was identified to be tumor-related p63-regulated gene 1 protein. Full article
(This article belongs to the Special Issue Advances in Toxicity of Nanoparticles)
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Review

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35 pages, 782 KiB  
Review
Review and Evaluation of the Potential Health Effects of Oxidic Nickel Nanoparticles
by Sharlee L. More, Michael Kovochich, Tara Lyons-Darden, Michael Taylor, Alexandra M. Schulte and Amy K. Madl
Nanomaterials 2021, 11(3), 642; https://doi.org/10.3390/nano11030642 - 5 Mar 2021
Cited by 19 | Viewed by 3082
Abstract
The exceptional physical and chemical properties of nickel nanomaterials have been exploited in a range of applications such as electrical conductors, batteries, and biomaterials. However, it has been suggested that these unique properties may allow for increased bioavailability, bio-reactivity, and potential adverse health [...] Read more.
The exceptional physical and chemical properties of nickel nanomaterials have been exploited in a range of applications such as electrical conductors, batteries, and biomaterials. However, it has been suggested that these unique properties may allow for increased bioavailability, bio-reactivity, and potential adverse health effects. Thus, the purpose of this review was to critically evaluate data regarding the toxicity of oxidic nickel nanoparticles (nickel oxide (NiO) and nickel hydroxide (Ni(OH)2) nanoparticles) with respect to: (1) physico-chemistry properties; (2) nanomaterial characterization in the defined delivery media; (3) appropriateness of model system and translation to potential human effects; (4) biodistribution, retention, and clearance; (5) routes and relevance of exposure; and (6) current research data gaps and likely directions of future research. Inhalation studies were prioritized for review as this represents a potential exposure route in humans. Oxidic nickel particle size ranged from 5 to 100 nm in the 60 studies that were identified. Inflammatory responses induced by exposure of oxidic nickel nanoparticles via inhalation in rodent studies was characterized as acute in nature and only displayed chronic effects after relatively large (high concentration and long duration) exposures. Furthermore, there is no evidence, thus far, to suggest that the effects induced by oxidic nickel nanoparticles are related to preneoplastic events. There are some data to suggest that nano- and micron-sized NiO particles follow a similar dose response when normalized to surface area. However, future experiments need to be conducted to better characterize the exposure–dose–response relationship according to specific surface area and reactivity as a dose metric, which drives particle dissolution and potential biological responses. Full article
(This article belongs to the Special Issue Advances in Toxicity of Nanoparticles)
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