Special Issue "Advances in Nanotoxicology"

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

Deadline for manuscript submissions: 30 September 2020.

Special Issue Editors

Prof. Dr. Anne Kahru
Website
Guest Editor
Laboratory of Environmental Toxicology, National Institute of Chemical Physics and Biophysics (NICPB) Akadeemia tee 23 Tallinn 12618, Estonia
Interests: nanotoxicology, ecotoxicology, in vitro toxicology, antimicrobials
Assoc. Prof. Dr. Monika Mortimer
Website
Guest Editor
Institute of Environmental and Health Sciences, College of Quality and Safety Engineering, China Jiliang University, Hangzhou, Zhejiang, China
Interests: ecotoxicology; nanotoxicology; engineered nanomaterials; microbiology; mechanisms of toxicity

Special Issue Information

Dear Colleagues,

With increased requirement for novel materials to facilitate societal progress, nanomaterials have been at the forefront of industry and various applications for more than several decades. Another side of the coin is the safety of these nano-enabled products. Safety is of prime importance to the sustainability of any novel technological approach, including nanotechnology. Thus, the main areas of focus of nanotoxicology include: (i) safety assessment of novel nanomaterials; (ii) elucidating toxicity mechanisms of nanomaterials to enable safe-by-design product development, and (iii) discovery of novel biological properties of nanomaterials for applications such as water treatment, nanomedicines, and nanoagrochemicals. This Special Issue aims to provide an overview of the recent developments in nanotoxicology research, including but not limited to:

  • experimental and theoretical approaches such as high-throughput assays, omics methods, novel in vitro models, cell co-cultures, systems biology, and nanoinformatics approaches;
  • assessment of nanomaterial effects on novel endpoints such as microbiome, inter- and intracellular, -organismal or -species interactions, and plant, animal or human diseases;
  • elucidation of toxicity mechanisms of nanomaterials;
  • nanoecotoxicity testing in environmentally relevant conditions and at environmentally relevant nanomaterial concentrations and physicochemical states;
  • safety evaluation of novel nanomaterial applications in water treatment, agriculture, medicine, environmental remediation and other fields;
  • developments in computational toxicology of nanomaterials, including predictive modeling, development of read-across and QSAR models, models related to adverse outcome pathways (AOP), and others.

Prof. Dr. Anne Kahru
Assoc. Prof. Dr. Monika Mortimer
Guest Editors

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 papers will be 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 monthly 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 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
  • Nanosafety
  • Safety of nanomedicines
  • Safety of nanoagrochemicals
  • Biocompatibility
  • Nanoantimicrobials
  • Hazard and exposure assessment
  • Mechanisms of action
  • Computational toxicology

Published Papers (2 papers)

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Research

Open AccessArticle
Nanoparticulate Gels for Cutaneous Administration of Caffeic Acid
Nanomaterials 2020, 10(5), 961; https://doi.org/10.3390/nano10050961 - 18 May 2020
Abstract
Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been [...] Read more.
Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing anti-inflammatory, antimicrobial, and anticarcinogenic properties. The object of this investigation was the development of a formulation for caffeic acid cutaneous administration. To this aim, caffeic acid has been loaded in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency and 200 nm mean dimension, as assessed by photon correlation spectroscopy. With the aim to improve the consistence of the aqueous nanodispersions, different types of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized by X-ray and rheological analyses. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was eight-fold slower with respect to the aqueous solution. In addition, the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective role exerted by the nanoparticles. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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Open AccessArticle
A Metabolomic Approach for the In Vivo Study of Gold Nanospheres and Nanostars after a Single-Dose Intravenous Administration to Wistar Rats
Nanomaterials 2019, 9(11), 1606; https://doi.org/10.3390/nano9111606 - 12 Nov 2019
Cited by 1
Abstract
Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and [...] Read more.
Gold nanoparticles (AuNPs) are promising nanoplatforms for drug therapy, diagnostic and imaging. However, biological comparison studies for different types of AuNPs fail in consistency due to the lack of sensitive methods to detect subtle differences in the expression of toxicity. Therefore, innovative and sensitive approaches such as metabolomics are much needed to discriminate toxicity, specially at low doses. The current work aims to compare the in vivo toxicological effects of gold nanospheres versus gold nanostars (of similar ~40 nm diameter and coated with 11-mercaptoundecanoic acid) 24 h after an intravenous administration of a single dose (1.33 × 1011 AuNPs/kg) to Wistar rats. The biodistribution of both types of AuNPs was determined by graphite furnace atomic absorption spectroscopy. The metabolic effects of the AuNPs on their main target organ, the liver, were analyzed using a GC-MS-based metabolomic approach. Conventional toxicological endpoints, including the levels of ATP and reduced and oxidized glutathione, were also investigated. The results show that AuNPs preferentially accumulate in the liver and, to a lesser extent, in the spleen and lungs. In other organs (kidney, heart, brain), Au content was below the limit of quantification. Reduced glutathione levels increased for both nanospheres and nanostars in the liver, but ATP levels were unaltered. Multivariate analysis showed a good discrimination between the two types of AuNPs (sphere- versus star-shaped nanoparticles) and compared to control group. The metabolic pathways involved in the discrimination were associated with the metabolism of fatty acids, pyrimidine and purine, arachidonic acid, biotin, glycine and synthesis of amino acids. In conclusion, the biodistribution, toxicological, and metabolic profiles of gold nanospheres and gold nanostars were described. Metabolomics proved to be a very useful tool for the comparative study of different types of AuNPs and raised awareness about the pathways associated to their distinct biological effects. Full article
(This article belongs to the Special Issue Advances in Nanotoxicology)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Long-term toxicity of ZnO nanoparticles to Scenedesmus rubescens cultivated in semi-batch mode
Authors: Andriana F. Aravantinou, Fytoula Andreou and Ioannis D. Manariotis
Affiliation: Environmental Engineering Laboratory, Civil Engineering Department, University of Patras, Patras 26504, Greece
Abstract: The aim of this work was to investigate the long-term toxic effect of zinc oxide (ZnO) NPs on freshwater microalgae, in semi-batch experiments at two different hydraulic retention time (HRT) (20 and 40 days). Scenedesmus rubescens was used as freshwater microalgae model species and was exposed to a semi-continuous supply of ZnO NPs (0.081 mg/L) for a period of 28 d. Experiments were conducted under controlled environmental conditions in order to investigate the impact of the presence of ZnO NPs on the nutrient removal, biomass growth, and algal lipid content of S. rubescesns. Semi-continuous mode cultures showed that low ZnO NPs concentrations at an HRT of 40 days, did not have any negative effect on microalgae growth, after the 4th day of culture. In contrast, the low HRT (20 d) applied resulted in algal growth inhibition by the presence of ZnO NPs, up to 17.5%. The nutrient removal was analogous to the microalgae growth. The lipid content was in most cases higher with the presence of ZnO NPs. The highest lipid content was observed at the HRT of 40 days and was at 28.5 and 22.6% with and without ZnO NPs, respectively.

Title: Caffeic acid nanoparticulate gel for the treatment of cutaneous oxidative stress
Authors: Maddalena Sguizzato1, Francesca Ferrara1, Markus Drechsler2, Paolo Mariani3, Supandeep Singh Hallan1, Nicolas Huang4, Rita Cortesi1*, Nicola Marchetti1, Giuseppe Valacchi5-7 and Elisabetta Esposito1*
Affiliation: 1 Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy 2 Bavarian Polymerinstitute "Electron and Optical Microscopy" University of Bayreuth, Germany, 3 Dipartmento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy, 4 Institut Galien Paris-Sud, CNRS UMR 8612, Univ Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, Châtenay-Malabry, France 5 Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy * Correspondence: [email protected]; Tel.: +39/0532/455259
Abstract: Caffeic acid is a natural antioxidant, largely distributed in plant tissues and food sources, possessing antiinflammatory, antimicrobial and anticarcinogenic properties. The object of this study was the development of a formulation for caffeic acid cutaneous administration. To this aim caffeic acid has been encapsulated in solid lipid nanoparticles by hot homogenization and ultrasonication, obtaining aqueous dispersions with high drug encapsulation efficiency, a mean diameter of 200 nm and a long term stability, as evaluated by photon correlation spectroscopy. In order to improve the consistency of the aqueous nanodispersions, different type of polymers have been considered. Particularly, poloxamer 407 and hyaluronic acid gels containing caffeic acid have been produced and characterized for rheology and spreadability. A Franz cell study enabled to select poloxamer 407, being able to better control caffeic acid diffusion. Thus, a nanoparticulate gel has been produced by addition of poloxamer 407 to nanoparticle dispersions. Notably, caffeic acid diffusion from nanoparticulate gel was 28-fold slower with respect to the aqueous solution. In addition the spreadability of nanoparticulate gel was suitable for cutaneous administration. Finally, the antioxidant effect of caffeic acid loaded in nanoparticulate gel has been demonstrated by ex-vivo evaluation on human skin explants exposed to cigarette smoke, suggesting a protective effect provided by the nanoparticles.

Title: Coating-dependent effects of silver nanoparticles on tobacco seed germination and early growth
Authors: R. Biba, D. Matić, D. M. Lyons, P. Peharec Štefanić, P. Cvjetko, M. Tkalec, D. Pavoković, I. Letofsky-Papst and B. Balen
Affiliation: Sveučilište u Zagrebu, Prirodoslovno-Matematički Fakultet, Zagreb, Croatia
Abstract: Silver nanoparticles (AgNPs) are nowadays dominating nanomaterial in a variety of consumer products due to their well-known antibacterial and antifungal properties. To increase their stability, different surface coatings are used, which might influence their physical/chemical properties. There has been concern about possible environmental and health consequences due to their wide application. Since plants play a significant role in accumulation and biodistribution of many environmentally released substances, they are also very likely to be influenced by AgNPs. In this study we have investigated the stability of differently coated AgNPs in a solid nutrient medium, as well as their effect on germination and early growth of tobacco (Nicotiana tabacum L.), an important crop plant that is commonly used as a model organism in abiotic stress research. To determine possible differences in effects on germination and seedling growth between silver applied in the form of nanoparticles and its ionic form, seeds were also exposed to the same concentrations of AgNO3 as well as to combined treatments with cysteine, a ligand with a strong affinity for silver. Additionally, the effects of coating molecules (PVP and CTAB) alone were also examined. Coating-dependent effects of AgNP-PVP and AgNP-CTAB on tobacco germination and early growth were recorded. The uptake and accumulation of Ag in seedlings was equally efficient after exposure to both types of AgNPs. However, AgNP-PVP induced mild toxicity on early growth only at higher concentrations, while AgNP-CTAB caused severe negative effects on germination and growth parameters at all applied concentrations. Cysteine addition successfully alleviated AgNP-PVP-induced negative effects, which suggests that the toxic impact of PVP-coated AgNPs is mainly due to release of Ag+ ions. On the contrary, cysteine failed to significantly improve germination and growth parameters after exposure to AgNP-CTAB, which suggests that effects of CTAB-coated AgNPs can rather be ascribed to surface coating itself and that released Ag+ ions have only a minor contribution to its toxicity. The work described has not been published previously and this manuscript or any of its parts are not under consideration for publication anywhere.

Title: In vitro study of toxicity mechanisms of nanoscale zero-valent iron (nZVI) and released iron ions using earthworm cells
Authors: Jaroslav Semerad1,2, Natividad Isabel Navarro Pacheco1,3, Petra Prochazkova1, Martin Pivokonsky4 and Tomas Cajthaml1,2*
Affiliation: 1 Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ-142 20, Prague 4, Czech Republic 2 Institute for Environmental Studies, Faculty of Science, Charles University, Benátská 2, CZ-128 01, Prague 2, Czech Republic 3 First Faculty of Medicine, Charles University, Kateřinská 1660/32, CZ-121 08, Prague 2, Czech Republic 4 Institute of Hydrodynamics of the Czech Academy of Sciences, Pod Paťankou 30/5, CZ-166 12, Prague 6, Czech Republic *corresponding author
Abstract: In the past two decades, nanomaterials based on nanoscale zero-valent iron (nZVI) have ranked among the most used remediation agents for soil and groundwater cleanup. The high reducing efficiency of elemental iron (Fe0) allows fast and cost-efficient degradation or transformation of many organic and inorganic pollutants. Although worldwide applications bring promising results, effects on exposed organisms are still not well explored. The majority of current studies are dealing with toxicity toward microbes and less other organisms that could also be exposed to nZVI during its applications. A novel approach of using immune effector cells of the earthworm Eisenia andrei, i.e. amoebocytes, was applied in this work to study the toxicity mechanisms of nZVI. Toxicity of dissolved iron released during the exposition was also considered, as well as in context of nanoparticle aging. The impact of nZVI and associated iron ions was studied in vitro on the subcellular level using different toxicological approaches as immunological responses and oxidative stress. The results revealed an increase in reactive oxygen species production caused by nZVI exposure, leading to lipid peroxidation. Programmed cell death was detected, although necrosis did not occur upon the exposure to environmentally relevant nZVI concentrations. Further, a decreasing tendency in phagocytosis also confirmed sub-lethal adverse effects even after short-term exposition to relatively small doses.

Title: Omics approaches in nano(eco)toxicology
Authors: Maša Vodovnik
Affiliation: Biotechnical faculty, Jamnikarjeva ulica 101, SI-1000 Ljubljana, Slovenia
Abstract: Upcoming soon~

Title: in vitro and in vivo models for evaluating the oral toxicity of nanomedicines
Authors: Chunhua Yang
Affiliation: IBMS, Georgia State University, Atlanta, United States
Abstract: Upcoming soon~

Title: European nanomaterial regulation – registration and safety assessment requirements in a methodological landscape
Authors: Maria B. Nielsen1*, Lauge. P. W. Clausen1, Aiga Mackevica1, Anders Baun1, Steffen F. Hansen1
Affiliation: 1 Department of Environmental Engineering, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
Abstract: The European Union’s Annex revisions of its chemical legislation, adopted in 2018, establish specific provisions for nanomaterials. The new provisions introduce requirements for manufacturers, importers and downstream users to comply with regarding registration and safety assessment of nanomaterials and apply as of 1 January 2020. The European Chemicals Industry Council, together with others, has been critical to whether compliance with the new requirements are possible in practice, for instance arguing that some of the testing methods needed to fulfil the requirements are still under development. This study aims to assess the availability of methods needed to comply with the new regulatory provisions to nanomaterials. Scientific literature and relevant test guideline frameworks were reviewed to identify applicable methods which were evaluated and categorized as either ‘accredited test guideline’, ‘under development as accredited test guideline’, ‘established as standard method in scientific literature’, or ‘other method’. We find that while a substantial proportion of the methods needed to comply with the new regulatory provisions are available as accredited test guidelines, some are still under development or not available. Based on our analysis of methodological gaps, recommendations will be provided for prioritized future efforts to assist registrants meet their new legal obligations on nanomaterials.

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