Special Issue "Cytotoxicity of Nanoparticles"

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

Deadline for manuscript submissions: closed (20 October 2016)

Special Issue Editor

Guest Editor
Prof. Dr. Eleonore Fröhlich

Center for Medical Research, Medical University of Graz, Stiftingtalstr 24, Graz A-8010, Austria
Website | E-Mail
Phone: +43-316-3857-3011
Fax: +43-316-3857-3009
Interests: biological and toxicological evaluation of nanoparticles; development of physiologically relevant in-vitro models; cytotoxicity of Nanoparticles

Special Issue Information

Dear Colleagues,

Human exposure to nanomaterials is not restricted to a specific group of individuals, but affects the entire population because nanoparticles are present in the environment, integrated in food and consumer products, and present in the workplace. Depending on the type of exposure (dermal, respiratory, oral, intravenous, etc.) physicochemical properties of the particles, including protein corona formation and particle concentrations, that reach viable cells, differ. Particle characterization in the respective biological fluids, relevant exposure conditions, and cellular models and appropriate readout parameters are, therefore, of key importance for the physiological relevance of cytotoxicity testing.

This Special Issue focuses on the adverse cellular effects of nanoparticles, including particle changes in biological fluids, permeation across barriers, cellular interaction, cell uptake and mechanisms of cellular action in conventional and advanced culture models.

Prof. Dr. Eleonore Fröhlich
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 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 1200 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

  • agglomeration
  • cellular mechanisms
  • 3D culture
  • apoptosis
  • necrosis
  • gene regulation
  • signaling pathways
  • cellular uptake
  • oxidative stress
  • inflammation
  • protein corona

Published Papers (8 papers)

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Research

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Open AccessArticle Silver Nanoparticles in Orthopedic Applications: New Insights on Their Effects on Osteogenic Cells
Nanomaterials 2017, 7(6), 124; doi:10.3390/nano7060124
Received: 28 March 2017 / Revised: 16 May 2017 / Accepted: 24 May 2017 / Published: 27 May 2017
Cited by 1 | PDF Full-text (696 KB) | HTML Full-text | XML Full-text
Abstract
Infections of orthopedic implants are associated with high morbidity. The emergence of antibiotic resistant strains and the tendency of microbes to form biofilms on orthopedic devices prompt the individuation of novel antimicrobial agents. Silver nanoparticles represent an interesting alternative, but their effects on
[...] Read more.
Infections of orthopedic implants are associated with high morbidity. The emergence of antibiotic resistant strains and the tendency of microbes to form biofilms on orthopedic devices prompt the individuation of novel antimicrobial agents. Silver nanoparticles represent an interesting alternative, but their effects on bone cells need to be clarified. We focused on osteoblast-like cells and on bone marrow-mesenchymal stem cells and found that these cells are rather resistant to the cytotoxic effects of silver nanoparticles, with a half maximal inhibitory concentration around 25 µg/mL as detected by MTT assay. Within a month of treatment, osteoblast-like cells adapt to the presence of the nanoparticles by upregulating hsp70 as shown by western blot. Hsp70 overexpression correlates with the restoration of normal cell proliferation. No alterations in the extent and time requirements were detected in mesenchymal stem cell induced to differentiate in osteoblasts in the presence of silver nanoparticles. Because the concentrations of silver nanoparticles which show antimicrobial activity are lower than those exerting toxic effects on bone-forming cells in vitro, we suggest that silver nanoparticles might represent a challenging tool to fight infections in orthopedic implants. Full article
(This article belongs to the Special Issue Cytotoxicity of Nanoparticles)
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Open AccessArticle In Vitro Comparative Skin Irritation Induced by Nano and Non-Nano Zinc Oxide
Nanomaterials 2017, 7(3), 56; doi:10.3390/nano7030056
Received: 26 October 2016 / Revised: 25 January 2017 / Accepted: 28 February 2017 / Published: 4 March 2017
Cited by 1 | PDF Full-text (2070 KB) | HTML Full-text | XML Full-text
Abstract
This study was designed to determine whether nano-sized ZnO has the potential to cause acute cutaneous irritation using cultured HaCaT keratinocytes and a human skin equivalent as in vitro models, compared to non-nanomaterials. Commercial nano ZnO with different sizes (50 nm and 100
[...] Read more.
This study was designed to determine whether nano-sized ZnO has the potential to cause acute cutaneous irritation using cultured HaCaT keratinocytes and a human skin equivalent as in vitro models, compared to non-nanomaterials. Commercial nano ZnO with different sizes (50 nm and 100 nm) was characterized by dynamic light scattering (DLS) and microscopy (SEM) in different media. Nano ZnO reduced the cell viability of HaCaT in a dose-dependent and time-dependent manner, in a similar way to macro ZnO. However, the 3D-epidermis model revealed no irritation at 1 mg/mL after 24 h of exposure. In conclusion, nano-sized ZnO does not irritate skin, in a similar manner to non-nano ZnO. Full article
(This article belongs to the Special Issue Cytotoxicity of Nanoparticles)
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Open AccessArticle Synthesis, Characterization, and Biological Evaluation of Nanostructured Hydroxyapatite with Different Dimensions
Nanomaterials 2017, 7(2), 38; doi:10.3390/nano7020038
Received: 15 December 2016 / Revised: 25 January 2017 / Accepted: 29 January 2017 / Published: 15 February 2017
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Abstract
Nanosized hydroxyapatite (HA) is a promising candidate for a substitute for apatite in bone in biomedical applications. Furthermore, due to its excellent bone bioactivity, nanosized strontium-substituted HA (SrHA) has aroused intensive interest. However, the size effects of these nanoparticles on cellular bioactivity should
[...] Read more.
Nanosized hydroxyapatite (HA) is a promising candidate for a substitute for apatite in bone in biomedical applications. Furthermore, due to its excellent bone bioactivity, nanosized strontium-substituted HA (SrHA) has aroused intensive interest. However, the size effects of these nanoparticles on cellular bioactivity should be considered. In this study, nanosized HA and SrHA with different dimensions and crystallization were synthesized by hydrothermal methods. The phase, crystallization and chemical composition were analyzed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR), respectively. The morphology was observed under field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The degradation behaviors of the samples were monitored by determining the ions release profile with inductively coupled plasma mass spectrometry (ICP-MS). The releasing behavior of Ca2+ and Sr2+ showed that the degradation rate was proportional to the specific surface area and inversely proportional to crystallization. The in vitro experiment evaluated by MG63 cells showed that SrHA nanorods with a length greater than 100 nm had the best biological performance both in cell proliferation and differentiation (* p < 0.05 compared with HA-1 and SrHA-1; * p < 0.01 compared with HA-2). In addition, HA nanoparticles with a lower aspect ratio had better bioactivity than higher ones (* p < 0.05). This study demonstrated that nanosized HA and SrHA with subtle differences (including dimensions, crystallization, specific surface area, and degradation rate) could affect the cellular growth and thus might have an impact on bone growth in vivo. This work provides a view of the role of nano-HAs as ideal biocompatible materials in future clinical applications. Full article
(This article belongs to the Special Issue Cytotoxicity of Nanoparticles)
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Open AccessArticle Amorphous Silica Particles Relevant in Food Industry Influence Cellular Growth and Associated Signaling Pathways in Human Gastric Carcinoma Cells
Nanomaterials 2017, 7(1), 18; doi:10.3390/nano7010018
Received: 6 November 2016 / Revised: 30 December 2016 / Accepted: 4 January 2017 / Published: 13 January 2017
Cited by 1 | PDF Full-text (4533 KB) | HTML Full-text | XML Full-text
Abstract
Nanostructured silica particles are commonly used in biomedical and biotechnical fields, as well as, in cosmetics and food industry. Thus, their environmental and health impacts are of great interest and effects after oral uptake are only rarely investigated. In the present study, the
[...] Read more.
Nanostructured silica particles are commonly used in biomedical and biotechnical fields, as well as, in cosmetics and food industry. Thus, their environmental and health impacts are of great interest and effects after oral uptake are only rarely investigated. In the present study, the toxicological effects of commercially available nano-scaled silica with a nominal primary diameter of 12 nm were investigated on the human gastric carcinoma cell line GXF251L. Besides the analysis of cytotoxic and proliferative effects and the comparison with effects of particles with a nominal primary diameter of 200 nm, emphasis was also given to their influence on the cellular epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) signaling pathways—both of them deeply involved in the regulation of cellular processes like cell cycle progression, differentiation or proliferation. The investigated silica nanoparticles (NPs) were found to stimulate cell proliferation as measured by microscopy and the sulforhodamine B assay. In accordance, the nuclear level of the proliferation marker Ki-67 was enhanced in a concentration-dependent manner. At high particle concentrations also necrosis was induced. Finally, silica NPs affected the EGFR and MAPK pathways at various levels dependent on concentration and time. However, classical activation of the EGFR, to be reflected by enhanced levels of phosphorylation, could be excluded as major trigger of the proliferative stimulus. After 45 min of incubation the level of phosphorylated EGFR did not increase, whereas enhanced levels of total EGFR protein were observed. These results indicate interference with the complex homeostasis of the EGFR protein, whereby up to 24 h no impact on the transcription level was detected. In addition, downstream on the level of the MAP kinases ERK1/2 short term incubation appeared to affect total protein levels without clear increase in phosphorylation. Depending on the concentration range, enhanced levels of ERK1/2 phosphorylation were only observed after 24 h of incubation. Taken together, the present study demonstrates the potential of the tested silica particles to enhance the growth of gastric carcinoma cells. Although interference with the EGFR/MAPK cascade is observed, additional mechanisms are likely to be involved in the onset of the proliferative stimulus. Full article
(This article belongs to the Special Issue Cytotoxicity of Nanoparticles)
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Open AccessArticle Titanium Dioxide Nanoparticle-Biomolecule Interactions Influence Oral Absorption
Nanomaterials 2016, 6(12), 225; doi:10.3390/nano6120225
Received: 19 October 2016 / Revised: 14 November 2016 / Accepted: 21 November 2016 / Published: 29 November 2016
PDF Full-text (3601 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Titanium dioxide (TiO2) nanoparticles (NPs) have been widely applied in various industrial fields, such as electronics, packaging, food, and cosmetics. Accordingly, concerns about the potential toxicity of TiO2 NPs have increased. In order to comprehend their in vivo behavior and
[...] Read more.
Titanium dioxide (TiO2) nanoparticles (NPs) have been widely applied in various industrial fields, such as electronics, packaging, food, and cosmetics. Accordingly, concerns about the potential toxicity of TiO2 NPs have increased. In order to comprehend their in vivo behavior and potential toxicity, we must evaluate the interactions between TiO2 NPs and biomolecules, which can alter the physicochemical properties and the fate of NPs under physiological conditions. In the present study, in vivo solubility, oral absorption, tissue distribution, and excretion kinetics of food grade TiO2 (f-TiO2) NPs were evaluated following a single-dose oral administration to rats and were compared to those of general grade TiO2 (g-TiO2) NPs. The effect of the interactions between the TiO2 NPs and biomolecules, such as glucose and albumin, on oral absorption was also investigated, with the aim of determining the surface interactions between them. The intestinal transport pathway was also assessed using 3-dimensional culture systems. The results demonstrate that slightly higher oral absorption of f-TiO2 NPs compared to g-TiO2 NPs could be related to their intestinal transport mechanism by microfold (M) cells, however, most of the NPs were eliminated through the feces. Moreover, the biokinetics of f-TiO2 NPs was highly dependent on their interaction with biomolecules, and the dispersibility was affected by modified surface chemistry. Full article
(This article belongs to the Special Issue Cytotoxicity of Nanoparticles)
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Open AccessArticle The Dispersion State of Tangled Multi-Walled Carbon Nanotubes Affects Their Cytotoxicity
Nanomaterials 2016, 6(11), 219; doi:10.3390/nano6110219
Received: 5 August 2016 / Revised: 5 November 2016 / Accepted: 11 November 2016 / Published: 19 November 2016
Cited by 2 | PDF Full-text (1463 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The medical applications of carbon nanotubes (CNTs) have garnered much attention. However, evaluating the safety of CNTs remains difficult, and no consensus has been reached. Moreover, assessing the biosafety of multi-walled CNTs (MWCNTs), which can become tangled during manufacturing, is challenging because they
[...] Read more.
The medical applications of carbon nanotubes (CNTs) have garnered much attention. However, evaluating the safety of CNTs remains difficult, and no consensus has been reached. Moreover, assessing the biosafety of multi-walled CNTs (MWCNTs), which can become tangled during manufacturing, is challenging because they do not readily disperse. We studied how the dispersion state of tangled MWCNTs affects their cytotoxicity, using three sonicators. Flotube 9110 (FT9110), tangled MWCNTs, were dispersed in two dispersants (fetal bovine serum and polysorbate 80) using a new type of sonicator (PR-1) and two conventional sonicators. The size and cytotoxicity of the dispersed FT9110 were measured using the BEAS-2B human bronchial epithelial cell line. The PR-1 dispersed the FT9110 to agglomerates <200 nm in diameter; FT9110 dispersed with the PR-1 did not show cytotoxicity regardless of dispersant. The other sonicators dispersed the FT9110 to particles >1000 nm in diameter, and cytotoxicity depended on the dispersant. We found that excluding cells adhered to agglomerated FT9110 before evaluating cytotoxicity can lead to false-positive results. The PR-1 sonicator dispersed tangled FT9110 to many single fibers, which showed lower cytotoxicity than conventionally-sonicated MWCNTs. We suggest that dispersion state should be accounted for when evaluating the cytotoxicity of MWCNTs. Full article
(This article belongs to the Special Issue Cytotoxicity of Nanoparticles)
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Open AccessArticle Biosynthesis of Silver Nanoparticles Using Taxus yunnanensis Callus and Their Antibacterial Activity and Cytotoxicity in Human Cancer Cells
Nanomaterials 2016, 6(9), 160; doi:10.3390/nano6090160
Received: 12 May 2016 / Revised: 20 August 2016 / Accepted: 26 August 2016 / Published: 1 September 2016
Cited by 2 | PDF Full-text (4335 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plant constituents could act as chelating/reducing or capping agents for synthesis of silver nanoparticles (AgNPs). The green synthesis of AgNPs has been considered as an environmental friendly and cost-effective alternative to other fabrication methods. The present work described the biosynthesis of AgNPs using
[...] Read more.
Plant constituents could act as chelating/reducing or capping agents for synthesis of silver nanoparticles (AgNPs). The green synthesis of AgNPs has been considered as an environmental friendly and cost-effective alternative to other fabrication methods. The present work described the biosynthesis of AgNPs using callus extracts from Taxus yunnanensis and evaluated their antibacterial activities in vitro and potential cytotoxicity in cancer cells. Callus extracts were able to reduce silver nitrate at 1 mM in 10 min. Transmission electron microscope (TEM) indicated the synthesized AgNPs were spherical with the size range from 6.4 to 27.2 nm. X-ray diffraction (XRD) confirmed the AgNPs were in the form of nanocrystals. Fourier transform infrared spectroscopy (FTIR) suggested phytochemicals in callus extracts were possible reducing and capping agents. The AgNPs exhibited effective inhibitory activity against all tested human pathogen bacteria and the inhibition against Gram-positive bacteria was stronger than that of Gram-negative bacteria. Furthermore, they exhibited stronger cytotoxic activity against human hepatoma SMMC-7721 cells and induced noticeable apoptosis in SMMC-7721 cells, but showed lower cytotoxic against normal human liver cells (HL-7702). Our results suggested that biosynthesized AgNPs could be an alternative measure in the field of antibacterial and anticancer therapeutics. Full article
(This article belongs to the Special Issue Cytotoxicity of Nanoparticles)
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Review

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Open AccessReview Evaluating Adverse Effects of Inhaled Nanoparticles by Realistic In Vitro Technology
Nanomaterials 2017, 7(2), 49; doi:10.3390/nano7020049
Received: 21 December 2016 / Revised: 10 February 2017 / Accepted: 13 February 2017 / Published: 22 February 2017
Cited by 1 | PDF Full-text (1926 KB) | HTML Full-text | XML Full-text
Abstract
The number of daily products containing nanoparticles (NP) is rapidly increasing. NP in powders, dispersions, or sprays are a yet unknown risk for incidental exposure, especially at workplaces during NP production and processing, and for consumers of any health status and age using
[...] Read more.
The number of daily products containing nanoparticles (NP) is rapidly increasing. NP in powders, dispersions, or sprays are a yet unknown risk for incidental exposure, especially at workplaces during NP production and processing, and for consumers of any health status and age using NP containing sprays. We developed the nano aerosol chamber for in vitro toxicity (NACIVT), a portable instrument for realistic safety testing of inhaled NP in vitro and evaluated effects of silver (Ag) and carbon (C) NP—which belong to the most widely used nanomaterials—on normal and compromised airway epithelia. We review the development, physical performance, and suitability of NACIVT for short and long-term exposures with air-liquid interface (ALI) cell cultures in regard to the prerequisites of a realistic in vitro test system for inhalation toxicology and in comparison to other commercially available, well characterized systems. We also review doses applied to cell cultures in vitro and acknowledge that a single exposure to realistic doses of spark generated 20-nm Ag- or CNP results in small, similar cellular responses to both NP types and that cytokine release generally increased with increasing NP dose. Full article
(This article belongs to the Special Issue Cytotoxicity of Nanoparticles)
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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: A dispersed state of tangled multi-walled carbon nanotubes affects cytotoxicity
Authors: Hisao Haniu*
Abstract: We are currently studying the medical application of carbon nanotubes (CNTs), a major nanomaterial used in biomaterials. However, the evaluation of CNT safety remains difficult and without consensus. Moreover, multi-walled CNTs (MWCNTs), which can become tangled in the manufacturing process, are also challenging to assess for safety since they do not readily disperse. In this report, we succeeded in dispersing previously tangled MWCNTs following treatment with a new type of sonicator (PR-1 Nano Premixer; Thinky). The untangled MWCNTs dispersed fully and produced a different result on cytotoxicity than did conventionally sonicated tangled MWCNTs. We describe the effects of the two dispersion methods on the size of MWCNTs and their resulting cytotoxicity.

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