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Special Issue "Developmental and Reproductive Toxicity of Iron Oxide 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 (31 July 2015).

Special Issue Editors

Assoc. Prof. Dr. Yuping Bao
E-Mail Website
Guest Editor
Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, USA
Interests: magnetic nanoparticles; imaging-guided drug delivery; MRI
Special Issues and Collections in MDPI journals
Dr. Anna Cristina S. Samia
E-Mail Website
Guest Editor
Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, 44106 USA
Interests: Magnetic Nanoparticles and Nanocomposites, Magnetic Particle Imaging, Magnetic Hyperthermia, Nanotoxicity in Plant and Soil Microbes

Special Issue Information

Dear Colleagues,

Iron oxide NPs have been widely explored in various applications, such as drug delivery, imaging agents in magnetic resonance and magnetic particle imaging, soil and groundwater remediation, and as photocatalysts. All these applications lead to increased production of iron oxide nanoparticles, subsequently increasing their existing levels in the environment and human exposure. The increased exposure can impact upon society in many ways, such as potential risk to human health, in particular to pregnant women or babies. Moreover, the high level of iron may also impact plant growth and development, because iron is an essential nutrient to plants. Therefore, it is critically important to understand the developmental and reproductive toxicity, and the long-term effects of iron oxide nanoparticles. We invite field experts to submit their related work, fostering in-depth discussion of this critical issue. Suggested topics include but are not limited to

(1) developmental and reproductive toxicity of iron oxide nanoparticles on whole organisms, such as fly, fish, mouse, rat, etc.,

(2) toxicity studies using in vitro models, such as perfused human placenta, or other systems,

(3) characterization and quantification of nanoparticles in tissues,

(4) cellular models to study developmental and reproductive toxicity,

(5) nanoparticle effects on plant growth and development.

Dr. Yuping Bao and Dr. Anna Cristina S. Samia
Guest Editor

Manuscript Submission Information

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Keywords

  • iron oxide nanoparticles
  • developmental and reproductive toxicity
  • nanotoxicity

Published Papers (9 papers)

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Research

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Open AccessArticle
Effects of Iron-Oxide Nanoparticle Surface Chemistry on Uptake Kinetics and Cytotoxicity in CHO-K1 Cells
Int. J. Mol. Sci. 2016, 17(1), 54; https://doi.org/10.3390/ijms17010054 - 31 Dec 2015
Cited by 25
Abstract
Superparamagnetic iron-oxide nanoparticles (SPIONs) show great promise for multiple applications in biomedicine. While a number of studies have examined their safety profile, the toxicity of these particles on reproductive organs remains uncertain. The goal of this study was to evaluate the cytotoxicity of [...] Read more.
Superparamagnetic iron-oxide nanoparticles (SPIONs) show great promise for multiple applications in biomedicine. While a number of studies have examined their safety profile, the toxicity of these particles on reproductive organs remains uncertain. The goal of this study was to evaluate the cytotoxicity of starch-coated, aminated, and PEGylated SPIONs on a cell line derived from Chinese Hamster ovaries (CHO-K1 cells). We evaluated the effect of particle diameter (50 and 100 nm) and polyethylene glycol (PEG) chain length (2k, 5k and 20k Da) on the cytotoxicity of SPIONs by investigating cell viability using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The kinetics and extent of SPION uptake by CHO-K1 cells was also studied, as well as the resulting generation of intracellular reactive oxygen species (ROS). Cell toxicity profiles of SPIONs correlated strongly with their cellular uptake kinetics, which was strongly dependent on surface properties of the particles. PEGylation caused a decrease in both uptake and cytotoxicity compared to aminated SPIONs. Interestingly, 2k Da PEG-modifed SPIONs displayed the lowest cellular uptake and cytotoxicity among all studied particles. These results emphasize the importance of surface coatings when engineering nanoparticles for biomedical applications. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Open AccessArticle
Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity
Int. J. Mol. Sci. 2015, 16(12), 30251-30268; https://doi.org/10.3390/ijms161226231 - 18 Dec 2015
Cited by 16
Abstract
Iron oxide nanoparticles (NPs) are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. [...] Read more.
Iron oxide nanoparticles (NPs) are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR) (CD-1) mice were exposed to a single, low (10 mg/kg) or high (100 mg/kg) dose of positively-charged polyethyleneimine-Fe2O3-NPs (PEI-NPs), or negatively-charged poly(acrylic acid)-Fe2O3-NPs (PAA-NPs) during critical windows of organogenesis (gestation day (GD) 8, 9, or 10). A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges) and testes (positive only) of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42%) and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero). Alternatively, negatively-charged PAA-NPs induced fetal loss (22%) earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Open AccessArticle
Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells
Int. J. Mol. Sci. 2015, 16(11), 26280-26290; https://doi.org/10.3390/ijms161125960 - 03 Nov 2015
Cited by 14
Abstract
Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the [...] Read more.
Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEONLA-BSA), or with dextran (SEONDEX). Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Open AccessArticle
Developmental and Reproductive Effects of Iron Oxide Nanoparticles in Arabidopsis thaliana
Int. J. Mol. Sci. 2015, 16(10), 24174-24193; https://doi.org/10.3390/ijms161024174 - 13 Oct 2015
Cited by 21
Abstract
Increasing use of iron oxide nanoparticles in medicine and environmental remediation has led to concerns regarding exposure of these nanoparticles to the public. However, limited studies are available to evaluate their effects on the environment, in particular on plants and food crops. Here, [...] Read more.
Increasing use of iron oxide nanoparticles in medicine and environmental remediation has led to concerns regarding exposure of these nanoparticles to the public. However, limited studies are available to evaluate their effects on the environment, in particular on plants and food crops. Here, we investigated the effects of positive (PC) and negative (NC) charged iron oxide (Fe2O3) nanoparticles (IONPs) on the physiology and reproductive capacity of Arabidopsis thaliana at concentrations of 3 and 25 mg/L. The 3 mg/L treated plants did not show evident effects on seeding and root length. However, the 25 mg/L treatment resulted in reduced seedling (positive-20% and negative-3.6%) and root (positive-48% and negative-negligible) length. Interestingly, treatment with polyethylenimine (PEI; IONP-PC coating) also resulted in reduced root length (39%) but no change was observed with polyacrylic acid (PAA; IONP-NC coating) treatment alone. However, treatment with IONPs at 3 mg/L did lead to an almost 5% increase in aborted pollen, a 2%–6% reduction in pollen viability and up to an 11% reduction in seed yield depending on the number of treatments. Interestingly, the treated plants did not show any observable phenotypic changes in overall size or general plant structure, indicating that environmental nanoparticle contamination could go dangerously unnoticed. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Open AccessArticle
Iron Oxide and Titanium Dioxide Nanoparticle Effects on Plant Performance and Root Associated Microbes
Int. J. Mol. Sci. 2015, 16(10), 23630-23650; https://doi.org/10.3390/ijms161023630 - 05 Oct 2015
Cited by 37
Abstract
In this study, we investigated the effect of positively and negatively charged Fe3O4 and TiO2 nanoparticles (NPs) on the growth of soybean plants (Glycine max.) and their root associated soil microbes. Soybean plants were grown in a [...] Read more.
In this study, we investigated the effect of positively and negatively charged Fe3O4 and TiO2 nanoparticles (NPs) on the growth of soybean plants (Glycine max.) and their root associated soil microbes. Soybean plants were grown in a greenhouse for six weeks after application of different amounts of NPs, and plant growth and nutrient content were examined. Roots were analyzed for colonization by arbuscular mycorrhizal (AM) fungi and nodule-forming nitrogen fixing bacteria using DNA-based techniques. We found that plant growth was significantly lower with the application of TiO2 as compared to Fe3O4 NPs. The leaf carbon was also marginally significant lower in plants treated with TiO2 NPs; however, leaf phosphorus was reduced in plants treated with Fe3O4. We found no effects of NP type, concentration, or charge on the community structure of either rhizobia or AM fungi colonizing plant roots. However, the charge of the Fe3O4 NPs affected both colonization of the root system by rhizobia as well as leaf phosphorus content. Our results indicate that the type of NP can affect plant growth and nutrient content in an agriculturally important crop species, and that the charge of these particles influences the colonization of the root system by nitrogen-fixing bacteria. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Open AccessArticle
Characterization, Quantification, and Determination of the Toxicity of Iron Oxide Nanoparticles to the Bone Marrow Cells
Int. J. Mol. Sci. 2015, 16(9), 22243-22257; https://doi.org/10.3390/ijms160922243 - 14 Sep 2015
Cited by 13
Abstract
Iron oxide nanoparticles (IONPs) have been used to develop iron supplements for improving the bioavailability of iron in patients with iron deficiency, which is one of the most serious nutritional deficiencies in the world. Accurate information about the characteristics, concentration, and cytotoxicity of [...] Read more.
Iron oxide nanoparticles (IONPs) have been used to develop iron supplements for improving the bioavailability of iron in patients with iron deficiency, which is one of the most serious nutritional deficiencies in the world. Accurate information about the characteristics, concentration, and cytotoxicity of IONPs to the developmental and reproductive cells enables safe use of IONPs in the supplement industry. The objective of this study was to analyze the physicochemical properties and cytotoxicity of IONPs in bone marrow cells. We prepared three different types of iron samples (surface-modified iron oxide nanoparticles (SMNPs), IONPs, and iron citrate) and analyzed their physicochemical properties such as particle size distribution, zeta potential, and morphology. In addition, we examined the cytotoxicity of the IONPs in various kinds of bone marrow cells. We analyzed particle size distribution, zeta potential, iron levels, and subcellular localization of the iron samples in bone marrow cells. Our results showed that the iron samples were not cytotoxic to the bone marrow cells and did not affect the expression of cell surface markers and lipopolysaccharide (LPS)-induced the secretion of cytokines by murine bone marrow-derived dendritic cells (BMDCs). Our results may be used to investigate the interactions between nanoparticles and cells and tissues and the developmental toxicity of nanoparticles. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Open AccessCommunication
Microwave-Induced Chemotoxicity of Polydopamine-Coated Magnetic Nanocubes
Int. J. Mol. Sci. 2015, 16(8), 18283-18292; https://doi.org/10.3390/ijms160818283 - 06 Aug 2015
Abstract
Polydopamine-coated FeCo nanocubes (PDFCs) were successfully synthesized and tested under microwave irradiation of 2.45 GHz frequency and 0.86 W/cm2 power. These particles were found to be non-toxic in the absence of irradiation, but gained significant toxicity upon irradiation. Interestingly, no increase in [...] Read more.
Polydopamine-coated FeCo nanocubes (PDFCs) were successfully synthesized and tested under microwave irradiation of 2.45 GHz frequency and 0.86 W/cm2 power. These particles were found to be non-toxic in the absence of irradiation, but gained significant toxicity upon irradiation. Interestingly, no increase in relative heating rate was observed when the PDFCs were irradiated in solution, eliminating nanoparticle (NP)-induced thermal ablation as the source of toxicity. Based on these studies, we propose that microwave-induced redox processes generate the observed toxicity. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Review

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Open AccessReview
In Vitro/In Vivo Toxicity Evaluation and Quantification of Iron Oxide Nanoparticles
Int. J. Mol. Sci. 2015, 16(10), 24417-24450; https://doi.org/10.3390/ijms161024417 - 15 Oct 2015
Cited by 57
Abstract
Increasing biomedical applications of iron oxide nanoparticles (IONPs) in academic and commercial settings have alarmed the scientific community about the safety and assessment of toxicity profiles of IONPs. The great amount of diversity found in the cytotoxic measurements of IONPs points toward the [...] Read more.
Increasing biomedical applications of iron oxide nanoparticles (IONPs) in academic and commercial settings have alarmed the scientific community about the safety and assessment of toxicity profiles of IONPs. The great amount of diversity found in the cytotoxic measurements of IONPs points toward the necessity of careful characterization and quantification of IONPs. The present document discusses the major developments related to in vitro and in vivo toxicity assessment of IONPs and its relationship with the physicochemical parameters of IONPs. Major discussion is included on the current spectrophotometric and imaging based techniques used for quantifying, and studying the clearance and biodistribution of IONPs. Several invasive and non-invasive quantification techniques along with the pitfalls are discussed in detail. Finally, critical guidelines are provided to optimize the design of IONPs to minimize the toxicity. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Open AccessReview
Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells
Int. J. Mol. Sci. 2015, 16(10), 23482-23516; https://doi.org/10.3390/ijms161023482 - 30 Sep 2015
Cited by 30
Abstract
In recent years, there has been an increased interest in the design and use of iron oxide materials with nanoscale dimensions for magnetic, catalytic, biomedical, and electronic applications. The increased manufacture and use of iron oxide nanoparticles (IONPs) in consumer products as well [...] Read more.
In recent years, there has been an increased interest in the design and use of iron oxide materials with nanoscale dimensions for magnetic, catalytic, biomedical, and electronic applications. The increased manufacture and use of iron oxide nanoparticles (IONPs) in consumer products as well as industrial processes is expected to lead to the unintentional release of IONPs into the environment. The impact of IONPs on the environment and on biological species is not well understood but remains a concern due to the increased chemical reactivity of nanoparticles relative to their bulk counterparts. This review article describes the impact of IONPs on cellular genetic components. The mutagenic impact of IONPs may damage an organism’s ability to develop or reproduce. To date, there has been experimental evidence of IONPs having mutagenic interactions on human cell lines including lymphoblastoids, fibroblasts, microvascular endothelial cells, bone marrow cells, lung epithelial cells, alveolar type II like epithelial cells, bronchial fibroblasts, skin epithelial cells, hepatocytes, cerebral endothelial cells, fibrosarcoma cells, breast carcinoma cells, lung carcinoma cells, and cervix carcinoma cells. Other cell lines including the Chinese hamster ovary cells, mouse fibroblast cells, murine fibroblast cells, Mytilus galloprovincialis sperm cells, mice lung cells, murine alveolar macrophages, mice hepatic and renal tissue cells, and vero cells have also shown mutagenic effects upon exposure to IONPs. We further show the influence of IONPs on microorganisms in the presence and absence of dissolved organic carbon. The results shed light on the OPEN ACCESS Int. J. Mol. Sci. 2015, 16 23483 transformations IONPs undergo in the environment and the nature of the potential mutagenic impact on biological cells. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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