Special Issue "Nanotoxicology"

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

Deadline for manuscript submissions: closed (31 March 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Robert Tanguay
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331-4003, USA
Website: http://emt.oregonstate.edu/roberttanguay
E-Mail: robert.tanguay@oregonstate.edu
Phone: +1 541 737 6514
Fax: +1 541 737 0497
Interests: developmental toxicity; high throughput screening; nanotoxicology; zebrafish; gene expression, miRNAs, and systems toxicology

Special Issue Information

Dear Colleagues,

Nanomaterial science continues to advance with the generation of more complex nanostructures with exciting potential applications. There have been parallel advances in the biological sciences aimed at evaluating the biocompatibility of these novel nanoparticles. Over recent years, we have realized that evaluating nanoparticles and biological interactions is quite complex because local environmental conditions influences particle behavior, and thus biocompatibility. In order to advance the development of safer high performing products, we need to understand the structural basis for these dynamic behaviors.

In this Special Issue, we are especially interested in manuscripts that advance the understanding of the specific nanomaterials attributes that govern or influence nanomaterial behavior and biocompatibility. This Issue invites manuscripts ranging from understanding dynamic behaviors of particles in aqueous environment, cellular toxicity, whole animal toxicity, neurotoxicity, immunotoxicity, genotoxicity, and population scale effects. Manuscripts that define specific biological responses at the organismal, gene expression, proteomic, and genetic levels are also invited.

Prof. Dr. Robert Tanguay
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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 quarterly 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 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • biocompatibility
  • nanotoxicology
  • in vivo
  • in vitro
  • predictive
  • nanotoxicity
  • safety assessment
  • nanoparticle characterization

Published Papers (3 papers)

Nanomaterials 2014, 4(2), 301-318; doi:10.3390/nano4020301
Received: 10 March 2014; in revised form: 15 April 2014 / Accepted: 15 April 2014 / Published: 22 April 2014
Show/Hide Abstract | Download PDF Full-text (1079 KB) | View HTML Full-text | Download XML Full-text

Nanomaterials 2014, 4(2), 203-221; doi:10.3390/nano4020203
Received: 7 February 2014; in revised form: 22 March 2014 / Accepted: 22 March 2014 / Published: 31 March 2014
Show/Hide Abstract | Download PDF Full-text (2618 KB) | Download XML Full-text

Nanomaterials 2014, 4(1), 175-188; doi:10.3390/nano4010175
Received: 6 January 2014; in revised form: 7 March 2014 / Accepted: 10 March 2014 / Published: 18 March 2014
Show/Hide Abstract | Download PDF Full-text (552 KB) | Download XML Full-text

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.

Type of Paper: Review
Title: Mechanisms underlying cytotoxicity induced by engineered nanomaterials: A review of in vitro studies
Authors:
Daniele R. Nogueira 1, Montserrat Mitjans 2 and M. Pilar Vinardell 2,*
Affiliations:

1Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
2Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain
Abstract:
Engineered nanomaterials are an emerging class of functional materials with technologically interesting properties and a wide range of promising applications, such as in drug delivery devices, medical imaging and diagnostics, and in other various industrial products. However, concerns have been expressed about the risks of such materials and whether they can cause adverse effects. Studies of the potential hazards of nanomaterials have been widely performed using cell models and a range of in vitro approaches. In the present review, we provide a comprehensive and critical literature overview on current in vitro toxicity test methods that have been applied to determine the mechanisms underlying the cytotoxic effects induced by the nanostructures. Nanomaterial features, such as small size, surface charge, hydrophobicity and high adsorption capacity, allow specific interactions within cell membrane and subcellular organelles, which in turn might lead to cytotoxicity through a range of different mechanisms. Finally, the given information on the relationships of nanomaterial cytotoxic responses with its structure and physicochemical properties might cooperate for the design of biologically safe nanostructures.

Type of Paper: Review
Title:
Autophagy as an underlying mechanism of nanoparticle toxicity?
Authors:
Vanessa Cohignac1,2,†, Marion Landry1,2, †, Jorge Boczkowski1,2 and Sophie Lanone1,2,*
Affiliations:

1
INSERM, U955, Equipe 4, Créteil, 94000, France
2
Université Paris Est-Créteil, Faculté de Médecine, Créteil, 94000, France
Abstract:
The rapid development of nanotechnologies is raising safety concerns because of the potential effects of the engineered nanomaterials on human health, particularly on the respiratory tract. Since the last decades, many in vivo studies have been interested in the pulmonary effects of different classes of nanomaterials. It has been shown that some of them can induce toxic effects, depending on their physico-chemical characteristics, but other studies did not identify any effects. Inflammation and oxidative stress are currently the two main mechanisms described as explaining the observed toxicity. However, the exact underlying mechanism(s) still remain(s) unknown. In this review, we will first summarize what is known about the respiratory effects of nanomaterials and we will then discuss the possible involvement of autophagy in this toxicity. Autophagy is a physiological process in which cytoplasmic components are digested via a lysosomal pathway. It has been shown that autophagy is involved in the pathogenesis and the progression of human diseases, and is able to modulate the oxidative stress and pro-inflammatory responses. A growing amount of literature suggests that a link between nanomaterials toxicity and autophagy impairment could exist. We will discuss the underlying potential mechanisms. At early steps, the autophagy process can be modulated i.e. by a modification of the mTOR-Akt pathway. Moreover, the lysosome being necessary in the final step of autophagy, autophagy impairment could be explained by a lysosomal dysfunction, a disruption of the lysosomal trafficking and/or a disruption of the cytoskeleton. This review should help to understand why autophagy impairment could be taken as a promising candidate to fully understand nanomaterials toxicity.
Keywords
: Nanomaterials, inflammation, oxidative stress, autophagy, lysosomes

Type of Paper: Review
Title:
Magnetite Nanoparticles Induce Genotoxicity in the Lung of Mice via Inflammatory Response
Authors:
Yukari Totsuka 1, Kousuke Ishino 1, Tatsuya Kato 1,7, Sumio Goto 2, Yukie Tada 3, Dai Nakae 3,4, Masatoshi Watanabe 5 and Keiji Wakabayashi 6,*
Affiliations:
1
Division of Cancer Development System, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
2
Laboratory of Environmental Risk Evaluation, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Chuou-ku, Sagamihara, Kanagawa 252-5201, Japan
3
Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Insitute of Public Health, 3-24-1 Hyakunin’cho, Shin’juku, Tokyo 169-0073, Japan, 1-1-1 Sakura-ga-Oka, Setagaya, Tokyo 156-8502, Japan
4
Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan, 6Division of Materials Science and Engineering, Graduate School of Engineering
5
Yokohama National University, Hodogaya-ku, Yokohama, Japan
6
Graduate Division of Nutritional and Environmental Sciences, University of Shizuoka, 52-1, Yada, Shizuoka 422-8526, Japan
Abstract:
Nanomaterials are useful for their characteristic properties, and are commonly used in various fields. Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and the genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice, and revealed that DNA damage analyzed by a comet assay in the lung of ICR mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately 2- to 3- fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency in the lungs of the four consecutive doses of 0.2 mg MGT exposed group was significantly higher than that of the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. Diffuse expression of inflammation marker, nitrotyrosine, was immunohistochemically observed in the lung of mice exposed to MGT. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72, 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2’-deoxyguanosine (8-OH-dG) and other adducts related DNA oxidative damage and inflammation responses were quantified by stable isotope dilution LC-MS/MS. Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lung of mice.
Keywords: magnetite nanoparticle, pulmonary inflammation, intratracheal instillation

Type of Paper: Article
Title:
Protein corona shows great protective effects towards cellular toxicity induced by carbon nanotube
Author:
Wenwan Zhong
Affiliations:
Department of Chemistry, University of California, Riverside, CA 92521, USA
Abstract:
Due to its unique physicochemical property, single walled carbon nanotubes (SWCNTs) have been widely recognized to be excellent one-dimensional nanomaterials that can be utilized in a vast number of fields, like electronics, optics, biosensor, drug delivery etc. However, concerns of its toxicity and safety have been raised and should be addressed. One possible way for SWCNTs to exert its toxicity is through binding with certain functional proteins inside cells, leading to the dysfunction of proteins and cellular pathways. Then, pre-coating the SWCNTs with a protein layer is a promising way to reduce its toxicity and protect functional proteins from being affected. In this paper, we adopt bovine serum albumin as a model protein to test its ability to reduce toxicity of SWCNTs. Our results show that BSA can reduce the toxicity based on its surface coverage ratio on SWCNTs, although cytosol proteins could compete off BSA from SWCNTs in a dose-dependent manner. HPLC-MS/MS was also used to identify the proteins that had strong affinity to the SWCNTs. Different patterns were found between different BSA coating ratios, which indicate that an additional protein layer influenced the binding of cellular proteins onto the SWCNTs that finally diminished the toxicity.

Type of Paper: Review
Title: Carbon Nanotubes: Are They Similar to Asbestos Fibers in Mechanisms of Toxicity and Disease Potential?
Author: Brooke T. Mossman
Affiliation: Department of Pathology, University of Vermont College of Medicine, 218 HSRF, 89 Beaumont Ave., Burlington, VT 05405, USA
Abstract: Single and multiwalled carbon nanotubes have attracted much attention due to their development by industry to generate heat and be used in a number of applications in nanomedicine, including drug delivery. They occur in a number of distinct shapes (tangled, helical and fiber-like), diameters, and lengths. In addition, nanotubes can be functionalized or modified on their external and internal surfaces and often contain a number of associated metals or other impurities. All of these features have been shown to be important in cell damage and other responses in vitro, inflammatory reactions in lung and pleural tissues, and potential to elicit fibrogenic and carcinogenic effects in experimental animal models. Some studies have suggested that carbon nanotubes, primarily those with a needle-like shape and high durability, may cause increases in lung cancer and mesothelioma in a manner similar mechanistically to amphibole asbestos fibers whereas others report less or no biological reactivity. In this review, we will discuss the mechanisms of action reported by us and others of asbestos fibers on lung epithelial and mesothelial cells that are linked to their pathogenicity in the development of lung cancers and mesotheliomas. We will then review the available literature on toxicity and carcinogenicity of carbon nanotubes with an emphasis on inhalation models of inflammation and disease as the most relevant and physiologic means of natural exposure. These experimental studies reveal that the magnitude of cell injury and disease potential is associated with high aspect-ratio, durable nanotubes although dose-response studies at levels potentially encountered by humans are lacking.

Type of Paper: Article
Title: The potential benefits and limitations of different test procedures to determine the effects of Ag nanomaterials and AgNO3 on soil nitrification activity
Author: Kerstin Hund-Rinke and Brigitte Peine Affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology, Auf dem Aberg 1, Schmallenberg, 57392, Germany
Abstract: The procedure described in OECD TG 216 is used to assess the effects of chemicals on soil nitrifiers. We investigated whether additional nitrogen sources modify the effect on nitrification caused by two silver nanomaterials (differing in size and shape) and a soluble silver salt. We used three different test procedures: (i) nitrogen transformation using the complex organic nitrogen source lucerne (OECD TG 216), (ii) nitrogen transformation using the inorganic nitrogen source (NH4)2SO4 and (iii) ammonium oxidation (ISO 15685). The results were compared with carbon transformation (OECD 217). The standard nitrogen transformation test using lucerne suggested that the test materials had no effect on soil nitrifiers, whereas significant effects were identified with the other two test procedures. The absence of effects with lucerne probably reflected the sorption of Ag+ to the additional organic nitrogen source thus reducing its bioavailability or the surface sorption of the organic matter which in turn blocks silver nanomaterial oxidation sites. This common test is therefore less suitable for the detection of potential effects caused by silver nanomaterials and soluble silver salts and we instead recommend the use of an inorganic nitrogen source or a test for potential ammonium oxidation. The observed effects were not specific to nanomaterials. The time course of the effect in both the nitrogen transformation test based on (NH4)2SO4 and the potential ammonium oxidation test varied according to the test substance. This may be useful to determine the stability of silver nanomaterials, although further experiments are necessary to verify this hypothesis.

Type of Paper: Review
Title:
Toxicological Considerations for Nanohybrid Materials
Authors:
Navid B. Saleh 1, Nirupam Aich 1, Joseph Bisesi 2, Jaime Plazas Tuttle 1 and Tara Sabo-Attwood 2*
Affiliations:
1Department of Civil Architectural and Environmental Engineering, University of Texas at Austin, Austin, TX 78712
2
Department of Environmental and Global Health, Center for Human and Environmental Toxicology, University of Florida, Gainesville, FL 32611
Abstract:
Conjugation of multiple nanomaterials has become the focus of recent materials development.   This new material class is known as nanohybrids or ‘horizon nanomaterials’.  Conjugation of metal/metal oxides with carbonaceous nanomaterials, overcoating or doping of one metal with another, have been pursued to enhance material performance and/or incorporate multifunctionality into nano-enabled devices and processes.  Nanohybrids are already used in commercialized energy, electronics, and medical products, which warrant immediate attention for safety evaluation.  These conjugated ensembles present a new set of physicochemical properties that are unique to their individual component attributes, hence increase uncertainty in their risk evaluation.  The established toxicological paradigms and enumerated underlying mechanisms will thus likely need to be reevaluated for these horizon materials.  This review article will present a critical discussion on altered physicochemical properties of nanohybrids and analyze the validity of existing nanotoxicology paradigms against these unique properties.  The article will also propose strategies to evaluate the conjugate material safety to help undertake future toxicological research on the nanohybrid material class.

Type of Paper: Review
Title:
Carbon Nanotubes and Chronic Granulomatous Lung Disease
Authors:
Mary Jane Thomassen * and Barbara Barna
Affiliation:
Division of Pulmonary, Critical Care and Sleep Medicine, Brody School of Medicine, 600 Moye Boulevard, 3E-149, East Carolina University, Greenville, NC 27834, USA
Abstract:
Use of nanomaterials in manufactured consumer products is a rapidly expanding industry and potential toxicities are just beginning to be explored.  Combustion-generated multiwall carbon nanotubes (MWCNT) or nanoparticles are ubiquitous in non-manufacturing environments and detectable in vapors from diesel fuel, methane, propane, and natural gas.  In experimental animal models, carbon nanotubes have been shown to induce granulomas or other inflammatory changes.  Evidence suggesting potential involvement of carbon nanomaterials in human granulomatous disease has been gathered from analyses of dusts generated in the World Trade Center disaster combined with the subsequent increase in granulomatous disease of first responders.  In this review we will discuss evidence for similarities in the pathophysiology of carbon nanotube-induced pulmonary disease in experimental animals with that of human granulomatous disease.

Type of Paper: Article
Title:
Reproductive Toxicity and Life History Study of Silver Nanoparticle Effect, Uptake and Transport in Arabidopsis thaliana
Authors:
Jane Geisler-Lee1,*, Jacob R. Gerfen1, Marjorie Brooks2, Qiang Wang3, Christin Fotis1, Anthony Sparer1, Xingmao Ma3, R. Howard Berg4, Matt Geisler1*
Affiliations:
1Department of Plant Biology, Southern Illinois University Carbondale, Carbondale, IL 62901, USA
2
Department of Zoology, Southern Illinois University Carbondale, Carbondale, IL 62901, USA
3
Department of Civil and Environmental Engineering, Southern Illinois University Carbondale, Carbondale, IL 62901, USA
4
Integrated Microscopy Facility, The Donald Danforth Plant Science Center, St. Louis, MO63132, USA
Abstract:
The concern of nanotechnology-enabled products has gradually led to understand how the release of engineered nanoparticles impacts in our environment. Geisler-Lee et al (2012) first demonstrated silver nanoparticles (AgNPs) accumulated in the root tips and transported through intercellular space of the plant Arabidopsis thaliana, and AgNPs could be viewed and tracked by light scattering in different microscopy. The impacts of 20 nm AgNPs in the life history traits of Arabidopsis plants were studied in both above- and belowground parts at two levels, gross phenotypes and routes of transport and accumulation in tissues from roots to shoots. Arabidopsis plants regularly irrigated with 75 g//AgNPs in soil did not show obvious phenotypes, but their vegetative development was prolonged and their reproductive growth shortened. In addition, the germination rates of their sequential offsprings drastically decrease over four generations. These traits confirmed that AgNPs were an abiotic stressor and caused reproductive toxicity to Arabidopsis. An Arabidopsis reporter line with green fluorescence protein growing in an optical transparent gel medium with 75 g/AgNPs showed the transport of AgNPs showed these routes: (1) AgNPs attached on the surface of primary roots and then entered their root tips; (2) As primary roots grew longer with root hairs and lateral root primordia, AgNPs not only gradually moved into vascular system but also entered new root primordia and root hairs; (3) When the Arabidopsis root system expanded to have multiple lateral roots, AgNPs were already present throughout the whole plant, from roots to shoots. In some cases, if cotyledons of the Arabidopsis seedlings were immersed in melt gellan gum, AgNPs could be seen in cotyledon, taken in by and accumulated in stomata cells.
Keywords
: Arabidopsis thaliana, silver nanoparticles, life history traits, transport

Last update: 27 January 2014

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