Neurodegenerative effects of air pollutant Particles: Biological mechanisms implicated for Early-Onset Alzheimer's disease.

BACKGROUND: Sporadic Alzheimer's disease (AD) occurs in 99% of all cases and can be influenced by air pollution such as diesel emissions and more recently, an iron oxide particle, magnetite, detected in the brains of AD patients. However, a mechanistic link between air pollutants and AD development remains elusive. AIM: To study the development of AD-relevant pathological effects induced by air pollutant particle exposures and their mechanistic links, in wild-type and AD-predisposed models. METHODS: C57BL/6 (n = 37) and APP/PS1 transgenic (n = 38) mice (age 13 weeks) were exposed to model pollutant iron-based particle (Fe0-Fe3O4, dTEM = 493 ± 133 nm), hydrocarbon-based diesel combustion particle (43 ± 9 nm) and magnetite (Fe3O4, 153 ± 43 nm) particles (66 µg/20 µL/third day) for 4 months, and were assessed for behavioural changes, neuronal cell loss, amyloid-beta (Aß) plaque, immune response and oxidative stress-biomarkers. Neuroblastoma SHSY5Y (differentiated) cells were exposed to the particles (100 µg/ml) for 24 h, with assessments on immune response biomarkers and reactive oxygen species generation. RESULTS: Pollutant particle-exposure led to increased anxiety and stress levels in wild-type mice and short-term memory impairment in AD-prone mice. Neuronal cell loss was shown in the hippocampal and somatosensory cortex, with increased detection of Aß plaque, the latter only in the AD-predisposed mice, with the wild-type not genetically disposed to form the plaque. The particle exposures however, increased AD-relevant immune system responses, including inflammation, in both strains of mice. Exposures also stimulated oxidative stress, although only observed in wild-type mice. The in vitro studies complemented the immune response and oxidative stress observations. CONCLUSIONS: This study provides insights into the mechanistic links between inflammation and oxidative stress to pollutant particle-induced AD pathologies, with magnetite apparently inducing the most pathological effects. No exacerbation of the effects was observed in the AD-predisposed model when compared to the wild-type, indicating a particle-induced neurodegeneration that is independent of disease state.

Ecotoxicological assessment of magnetite and magnetite/Ag nanoparticles on terrestrial and aquatic biota from different trophic levels.

The aim of the study is an ecotoxicological assessment of magnetite iron oxide-based nanoparticles (NPs), which have risen in popularity in the last decade, on selected terrestrial and aquatic organisms from various levels of the food chain. In the presented study various organisms, from both the terrestrial and aquatic environment, were used as targets for the assessment of NPs ecotoxicity. Plants (radish, oat), marine bacteria (A. fischeri) and crustacean (H. incongruens) were used to represent producers, decomposers, and consumers, respectively. It was found that examined NPs were harmful (to a different degree) to biota from three different trophic levels. Physicochemical characterization (size/morphology, crystallinity, composition, and magnetic properties) of the tested nanoparticles was performed by: transmission electron microscopy, X-ray diffraction, energy dispersive spectroscopy, and Mossbauer spectroscopy, respectively. Phytotoxicity was evaluated according to the OECD 208 Guideline, while acute and chronic toxicity of NPs was conducted using bioassays employing bacteria and crustacea, respectively. The phytotoxicity of all investigated iron oxide-based NPs was dependent on concentration and type of NPs formulation and was measured via biomass, seed germination, root length, shoot height, and content of plant pigments. Increasing the concentration of NPs increased phytotoxicity and mortality of aquatic organisms. Ecotoxicity of iron oxide/silver was dependent on the size and content of silver. Iron oxide NPs coated with nanosilver in a percentage ratio of 69/31 were found to be the most toxic on tested terrestrial and aquatic biota.

Photocatalytic Degradation of 4,4'-Isopropylidenebis(2,6-dibromophenol) on Magnetite Catalysts vs. Ozonolysis Method: Process Efficiency and Toxicity Assessment of Disinfection By-Products.

Flame retardants have attracted growing environmental concern. Recently, an increasing number of studies have been conducted worldwide to investigate flame-retardant sources, environmental distribution, living organisms' exposure, and toxicity. The presented studies include the degradation of 4,4'-isopropylidenebis(2,6-dibromophenol) (TBBPA) by ozonolysis and photocatalysis. In the photocatalytic process, nano- and micro-magnetite (n-Fe3O4 and µ-Fe3O4) are used as a catalyst. Monitoring of TBBPA decay in the photocatalysis and ozonolysis showed photocatalysis to be more effective. Significant removal of TBBPA was achieved within 10 min in photocatalysis (ca. 90%), while for ozonation, a comparable effect was observed within 70 min. To determine the best method of TBBPA degradation concentration on COD and TOC, the removals were examined. The highest oxidation state was obtained for photocatalysis on µ-Fe3O4, whereas for n-Fe3O4 and ozonolysis, the COD/TOC ratio was lower. Acute toxicity results show noticeable differences in the toxicity of TBBPA and its degradation products to Artemia franciscana and Thamnocephalus platyurus. The EC50 values indicate that TBBPA degradation products were toxic to harmful, whereas the TBPPA and post-reaction mixtures were toxic to the invertebrate species tested. The best efficiency in the removal and degradation of TBBPA was in the photocatalysis process on µ-Fe3O4 (reaction system 1). The examined crustaceans can be used as a sensitive test for acute toxicity evaluation.

In vitro cytotoxicity study of superparamagnetic iron oxide and silica nanoparticles on pneumocyte organelles.

Inhalation is the main route of nanoparticles (NP) exposure during manufacturing. Although many mechanisms of toxicity have been described, the interaction of NP with relevant pneumocytes organelles is not widely understood. Considering that the physicochemical properties of NP influence their toxicological responses, the objective of this study was to evaluate whether exposure to different NP, crystalline Fe3O4 NP and amorphous SiO2 NP could alter pneumocytes organelles in alveolar epithelial cells. To achieve this goal, cell viability, ultrastructural changes, lysosomal damage, mitochondrial membrane potential (MMP), lipid droplets (LD) formation and cytokines production were evaluated by MTT, electron microscopy, lysotracker red staining, JC-1, Oil Red staining and Milliplex® assay respectively. Both NP were observed within lamellar bodies (LB), lysosomes, and cytoplasm causing morphological changes. Exposure to SiO2 NP at 6 h induced lysosomal activation, but not Fe3O4 NP. MMP decreased and LD increased at the highest concentrations after both NP exposure. Pro-inflammatory cytokines were released only after SiO2 NP exposure at 48 h. These results indicate that SiO2 NP have a greater impact than Fe3O4 NP on organelles responsible for energy, secretion, degradation and metabolism in pneumocytes leading to the development of respiratory disorders or the exacerbation of preexisting conditions. Therefore, the established biocompatibility for amorphous NP has to be reconsidered.

Comparison of respiratory toxicity of TiO2 and Fe3O4 nanoparticles after intravenous instillation: an experimental study.

OBJECTIVE: Nanomaterials consist of particles smaller than 100 nm - nanoparticles (NPs). Their nano dimensions allow them to penetrate through various membranes and enter into the bloodstream and disseminate into different body organs. Massive expansion of nanotechnologies together with production of new nanoparticles which have not yet been in contact with living organisms may pose a potential health problem. It is therefore necessary to investigate the health impact of NPs after experimental exposure. Comparison of the effect of TiO2 and NPs Fe3O4 in Wistar rats at time intervals 1, 7, 14 and 28 days was performed by studying the cytotoxic effect in the isolated inflammatory cells from bronchoalveolar lavage (BAL). METHODS: Wistar rats were intravenously (i.v.) given a suspension of NPs TiO2 or Fe3O4 (coated by sodium oleate) via the tail vein. After time intervals of 1, 7, 14 and 28 days, we sacrificed the animals under anaesthesia, performed BAL and isolated the cells. The number of animals in the individual groups was 7-8. We examined the differential count of BAL cells (alveolar macrophages - AM, polymorphonuclear leukocytes - PMN, lymphocytes - Ly); viability and phagocytic activity of AM; the proportion of immature and polynuclear cells and enzymes - cathepsin D - CAT D, lactate dehydrogenase - LDH and acid phosphatase - ACP. RESULTS: We found that TiO2 NPs are relatively inert - without induction of inflammatory and cytotoxic response. Exposure to nanoparticles Fe3O4 induced - under the same experimental conditions - in comparison with the control and TiO2 a more extensive inflammatory and cytotoxic response, albeit only at 1, 7 and 14 days after injection. CONCLUSIONS: The results suggest that TiO2 and Fe3O4 nanoparticles used in our study were transferred from the bloodstream to the respiratory tract, but this effect was not observed at 28 days after i.v. injection, probably due to their removal from the respiratory tract.

Changes of root microbial populations of natively grown plants during natural attenuation of V-Ti magnetite tailings.

Mine tailings contain dangerously high levels of toxic metals which pose a constant threat to local ecosystems. Few naturally grown native plants can colonize tailings site and the existence of their root-associated microbial populations is poorly understood. The objective of this study was to give further insights into the interactions between native plants and their microbiota during natural attenuation of abandoned V-Ti magnetite mine tailings. In the present work, we first examined the native plants' potential for phytoremediation using plant/soil analytical methods and then investigated the root microbial communities and their inferred functions using 16 S rRNA-based metagenomics. It was found that in V-Ti magnetite mine tailings the two dominant plants Bothriochloa ischaemum and Typha angustifolia were able to increase available nitrogen in the rhizosphere soil by 23.3% and 53.7% respectively. The translocation factors (TF) for both plants indicated that B. ischaemum was able to accumulate Pb (TF = 1.212), while T. angustifolia was an accumulator of Mn (TF = 2.502). The microbial community structure was more complex in the soil associated with T. angustifolia than with B. ischaemum. The presence of both plants significantly reduced the population of Acinetobacter. Specifically, B. ischaemum enriched Massilia, Opitutus and Hydrogenophaga species while T. angustifolia significantly increased rhizobia species. Multivariate analyses revealed that among all tested soil variables Fe and total organic carbon (TOC) could be the key factors in shaping the microbial structure. The putative functional analysis indicated that soil sample of B. ischaemum was abundant with nitrate/nitrite reduction-related functions while that of T. angustifolia was rich in nitrogen fixing functions. The results indicate that these native plants host a diverse range of soil microbes, whose community structure can be shaped by plant types and soil variables. It is also possible that these plants can be used to improve soil nitrogen content and serve as bioaccumulators for Pb or Mn for phytoremediation purposes.

Development and Assessment of Nano-Technologies for Cancer Treatment: Cytotoxicity and Hyperthermia Laboratory Studies.

Cancer treatment by magnetic hyperthermia offers numerous advantages, but for practical applications many variables still need to be adjusted before developing a controlled and reproducible cancer treatment that is bio-compatible (non-damaging) to healthy cells. In this work, Fe3O4 and CoFe2O4 were synthesized and systematically studied for the development of efficient therapeutic agents for applications in hyperthermia. The biocompatibility of the materials was further evaluated using HepG2 cells as biological model. Colorimetric and microscopic techniques were used to evaluate the interaction of magnetic nano-materials (MNMs) and HepG2 cells. Finally, the behavior of MNMs was evaluated under the influence of an alternating magnetic field (AMF), observing a more efficient temperature increment for CoFe2O4, a desirable behavior for biomedical applications since lower doses and shorter expositions to alternating magnetic field might be required.

Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles.

Iron nanoparticles (NPs) have been proposed as a tool in very different fields such as environmental remediation and biomedical applications, including food fortification against iron deficiency, even if there is still concern about their safety. Here, we propose Xenopus laevis embryos as a suitable model to investigate the toxicity and the bio-interactions at the intestinal barrier of Fe3O4 and zerovalent iron (ZVI) NPs compared to Fe(II) and (III) salts in the 5 to 100 mg Fe/L concentration range using the Frog Embryo Teratogenesis Assay in Xenopus (FETAX). Our results demonstrated that, at concentrations at which iron salts induce adverse effects, both iron NPs do not cause acute toxicity or teratogenicity even if they accumulate massively in the embryo gut. Prussian blue staining, confocal and electron microscopy allowed mapping of iron NPs in enterocytes, along the paracellular spaces and at the level of the basement membrane of a well-preserved intestinal epithelium. Furthermore, the high bioaccumulation factor and the increase in embryo length after exposure to iron NPs suggest greater iron intake, an essential element for organisms. Together, these results improve the knowledge on the safety of orally ingested iron NPs and their interaction with the intestinal barrier, useful for defining the potential risks associated with their use in food/feed fortification.

Investigation of the effect of magnetite iron oxide particles size on cytotoxicity in A549 cell line.

INTRODUCTION: Magnetite as iron oxide is widely used in various industries, in the pharmaceutical industry in particular where it is used for its magnetic properties. The environmental and occupational exposure to airborne nanoparticles and microparticles of iron oxide compounds have been reported. Since authors have reported contradictory results, the objective of this study was to investigate the effect of particles' size in their toxicities. METHODS: The human cell line A549 was exposed with magnetite iron oxide in two size categories of micro (≥5 µm) and nano (<100 nm), with four concentrations of 10, 50, 100, and 250 µg/ml at two time periods of 24 and 72 h. The cell viability, reactive oxygen species (ROS), changes in mitochondrial membrane potential, and incidence of apoptosis were studied. RESULTS: Nano and micro magnetite particles demonstrated diverse toxicity effects on the A549 cell line at the 24- and 72-h exposure periods; however, the effects produced were time- and concentration-dependent. Nano magnetite particles produced greater cellular toxicities in forms of decreased viabilities at concentration exposures greater than 50 µg/ml (p < 0.05), along with increased ROS (p < 0.05), decreased cellular membrane potential (p < 0.05), and reduced rate of apoptosis (p < 0.05). DISCUSSION: The results of this study demonstrated that magnetite iron in nano-range sizes had a greater absorbability for the A549 cell line compared to micro sizes, and at the same time, nanoparticles were more toxic than microparticles, demonstrating higher production of ROS and decreased viabilities. Considering the greater toxicity of nanoparticles of magnetite iron in this study, thorough precautionary control measures must be taken before they can be used in various industries.

Airborne Magnetite- and Iron-Rich Pollution Nanoparticles: Potential Neurotoxicants and Environmental Risk Factors for Neurodegenerative Disease, Including Alzheimer's Disease.

Fewer than 5% of Alzheimer's disease (AD) cases are demonstrably directly inherited, indicating that environmental factors may be important in initiating and/or promoting the disease. Excess iron is toxic to cells; iron overload in the AD brain may aggressively accelerate AD. Magnetite nanoparticles, capable of catalyzing formation of reactive oxygen species, occur in AD plaques and tangles; they are thought to form in situ, from pathological iron dysfunction. A recent study has identified in frontal cortex samples the abundant presence of magnetite nanoparticles consistent with high-temperature formation; identifying therefore their external, not internal source. These magnetite particles range from ∼10 to 150 nm in size, and are often associated with other, non-endogenous metals (including platinum, cadmium, cerium). Some display rounded crystal morphologies and fused surface textures, reflecting cooling and crystallization from an initially heated, iron-bearing source material. Precisely-matching magnetite 'nanospheres' occur abundantly in roadside air pollution, arising from vehicle combustion and, especially, frictional brake-wear. Airborne magnetite pollution particles < ∼200 nm in size can access the brain directly via the olfactory and/or trigeminal nerves, bypassing the blood-brain barrier. Given their toxicity, abundance in roadside air, and nanoscale dimensions, traffic-derived magnetite pollution nanoparticles may constitute a chronic and pernicious neurotoxicant, and hence an environmental risk factor for AD, for large population numbers globally. Olfactory nerve damage displays strong association with AD development. Reported links between AD and occupational magnetic fields (e.g., affecting welders, machinists) may instead reflect inhalation exposure to airborne magnetic nanoparticles.

Silica coated iron oxide nanoparticles-induced cytotoxicity, genotoxicity and its underlying mechanism in human HK-2 renal proximal tubule epithelial cells.

Iron oxide nanoparticles (IONPs) have a great potential with regard to cell labelling, cell tracking, cell separation, magnetic resonance imaging, magnetic hyperthermia, targeted drug and gene delivery. However, a growing body of research has raised concerns about the possible unwanted adverse cytotoxic effects of IONPs. In the present study, the in vitro cellular uptake, antiproliferative activity, cytotoxicity, genotoxicity, prooxidant, microtubule-disrupting and apoptosis-inducing effect of Fe3O4@SiO2 and passivated Fe3O4@SiO2-NH2 nanoparticles on human renal proximal tubule epithelial cells (HK-2) have been studied. Both investigated silica coated IONPs were found to have cell growth-inhibitory activity in a time- and dose-dependent manner. Determination of cell cycle phase distribution by flow cytometry demonstrated a G1 and G2/M phase accumulation of HK-2 cells. A tetrazolium salt cytotoxicity assay at 24 h following treatment demonstrated that cell viability was reduced in a dose-dependent manner. Microscopy observations showed that both Fe3O4@SiO2 and Fe3O4@SiO2-NH2 nanoparticles accumulated in cells and appeared to have microtubule-disrupting activity. Our study also revealed that short term 1 h exposure to 25 and 100 µg/mL of silica coated IONPs causes genotoxicity. Compared with vehicle control cells, a significantly higher amount of γH2AX foci correlating with an increase in DNA double-strand breaks was observed in Fe3O4@SiO2 and Fe3O4@SiO2-NH2-treated and immunestained HK-2 cells. The investigated nanoparticles did not trigger significant ROS generation and apoptosis-mediated cell death. In conclusion, these findings provide new insights into the cytotoxicity of silica coated IONPs that may support their further safer use.

In vitro toxicity assessment of zinc and nickel ferrite nanoparticles in human erythrocytes and peripheral blood mononuclear cell.

Ferrite nanoparticles (NPs) have gained attention in biomedicine due to their many potential applications, such as targeted drug delivery, their use as contrast agents for magnetic resonance imaging and oncological treatments. The information about the risk effects of ferrite NPs in human blood cells is, however, scarce. To assess their potential toxicity, in vitro studies were carried out with magnetite and zinc, nickel and nickel­zinc ferrites NPs at different concentrations (50, 100 and 200 µg·ml-1). The toxicity of the ferrite NPs was evaluated in humans by determining red blood hemolysis, by measuring the content of total proteins, and by assaying catalase and glutathione-S-transferase activities. Our results show that nickel­zinc ferrite lead to hemolysis, and that magnetite, zinc and nickel­zinc ferrites increase glutathione-S-transferase activity. No significant changes in human peripheral blood mononuclear cells viability were observed after the treatment with the four different ferrite NPs in vitro.

Biocompatible Fe3O4/chitosan scaffolds with high magnetism.

Durable and biocompatible magnetic scaffolds prepared by simple approaches are important for the development of tissue engineering. In this work, by freeze-drying method and without using any crosslinker, we successfully fabricated Fe3O4/chitosan magnetic scaffolds that belong to hard magnetic materials and are stable in physiological fluid. In vitro biocompatibility assay showed that mouse mesenchymal progenitor cells grow normally on the surface of the scaffolds. So these magnetic scaffolds have potentials to be used in tissue engineering as implants that independently direct drug targeting.

Toward comprehension of multiple human cells uptake of engineered nano metal oxides: quantitative inter cell line uptake specificity (QICLUS) modeling.

To address the nanomaterial exposure threat, it is imperative to understand how nanomaterials are recognized, internalized, and distributed within diverse cell systems. Targeting of nanomaterials to a specific cell type is generally attained through the modification of the nanoparticle (NP) surface leading to required cellular uptake. The enhanced cellular uptake to normal cells can direct to the higher interaction of NPs with subcellular organelles resulting the provocation of various signaling pathways. The successes of NPs rely on the prospect for the synthesis of functionalized NPs with necessary properties and their enhanced potential for cellular uptake for specific targeting. In the present study, we have modeled the cellular uptake of 109 surface modifiers of metal oxide nanoparticles (MNPs) for three different cell lines: HUVEC (Human endothelial cells), U937 (human macrophage cells), and PaCa2 (cancer cell lines). Along with the quantitative structure-activity relationship (QSAR) models, for the very first time we have developed and performed quantitative inter cell line uptake specificity (QICLUS) modeling to identify the physicochemical properties, as well as majorly structural fragments responsible for cellular uptake differences between two specific cell lines. The present work provides a comprehensive understanding of the cellular uptake of MNPs and the underlying structural parameters controlling the nano-cellular interactions. This phenomenon has also been analyzed from the QSAR and QICLUS models that concluded the functional groups of surface modifiers like amine, anhydride, halogen atoms, nitro group, acids have the dominating roles for the uptake of MNPs into the cell lines. Thus, the developed models may be used for designing of novel surface modifiers of MNPs of desired characteristics for proper cell-NPs interactions, as well as in the context of virtual screening aspect. Moreover, the MNP-cell interactions can give some idea about the toxicity for target-specific drug delivery treatment as higher cellular uptake is required for specific cells to treat the disease and lower uptake to the neighboring cells for lower toxicity.

Combined Toxicity of an Environmental Remediation Residue, Magnetite Fe3O4 Nanoparticles/Cr(VI) Adduct.

OBJECTIVE: This paper aims to elucidate the combined toxicity of magnetite nanoparticles/Chromium [MNPs/Cr(VI)] adducts. METHODS: The HEK293 cell was exposed to either Cr(VI) or MNPs, or their adducts MNPs/Cr(VI). The cytotoxicity was evaluated by assessing the cell viability, apoptosis, oxidative stress induction, and cellular uptake. RESULTS: The toxicity of formed adducts is significantly reduced when compared to Cr(VI) anions. We found that the cellular uptake of MNPs/Cr(VI) adduct was rare, only few particles were endocytosed from the extracellular fluid and not accumulated in the cell nucleus. On the other hand, the Cr(VI) anions entered cells, generated oxidative stress, induced cell apoptosis, and caused cytotoxicity. CONCLUSION: The results showed minor effects of the nanoadducts on the tested cells and supported that magnetite nanoparticles could be implemented in the wastewater treatment process in which advantageous properties outweigh the risks.

The elemental changes occurring in the rat liver after exposure to PEG-coated iron oxide nanoparticles: total reflection x-ray fluorescence (TXRF) spectroscopy study.

The main goal of this study was to evaluate in vivo effects of low dose of PEG-coated magnetic iron oxide nanoparticles (IONPs) on the rat liver. The IONPs was intravenously injected into rats at a dose equaled to 0.03 mg of Fe per 1 kg of an animal body weight. The elemental composition of liver tissue in rats subjected to IONPs action and controls were compared. Moreover, in order to determine the dynamics of nanoparticles (NPs) induced elemental changes, the tissues taken from animals 2 hours, 24 hours, and 7 days from IONPs injection were examined. The analysis of subtle elemental anomalies occurring as a result of IONPs action required application of highly sensitive analytical method. The total reflection X-ray fluorescence spectroscopy perfectly meets such requirements and therefore it was used in this study. The obtained results showed increasing trend of Fe level within liver occurring 2 hours from IONPs injection. One day after NPs administration, the liver Fe content presented the baseline level what suggests only the short-term accumulation of nanoparticles in the organ. The Ca, Cu, and Zn levels changed significantly as a result of NPs action. Moreover, the anomalies in their accumulation were still observed 7 days after IONPs injection. The level of Cu decreased while those of Ca and Zn increased in the liver of NPs-treated animals. The reduced liver Cu, followed by elevated serum level of this element, might be related in triggering the mechanisms responsible for Fe metabolism in the organism.

Developmental toxicity of Fe3O4 nanoparticles on cysts and three larval stages of Artemia salina.

Using Artemia salina cysts (capsulated and decapsulated) and larvae (instar I, II and III) as experimental models, the potential effects of Fe3O4 nanoparticles (Fe3O4-NPs) on marine ecosystems were investigated. Hatchability, mortality and a number of ethological, morphological and biochemical parameters were selected as end-points to define the toxic responses. Data showed that the hatching rates of capsulated and decapsulated cysts were significantly decreased (p < 0.01) following exposure to 600 mg/L for 24 and 36 h. The LC50 values for instar II and III were 482 and 561 mg/L (could not be measured for instar I), and the EC50 values for swimming inhibition of instar I, II and III were 474, 365 and 421 mg/L, respectively. Effects on hatchability, mortality and swimming were accounted for Fe3O4-NPs rather than iron ion released from the NPs. Instar II larvae showed the greatest sensitivity to Fe3O4-NPs, and followed by instar III, instar I, decapsulated cysts and capsulated cysts. Body lengths of instar I, II and III larvae were decreased in dose-dependent manners. Fe3O4-NPs attached onto the gills and body surface, resulting in irreversible damages. Reactive oxygen species, malondialdehyde content, total antioxidant capacity and antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) activities were substantially increased following exposure, indicating that toxic effects were related to oxidative stress. Mitochondrial malformation, cristae rupturing and membranous structure disruption were clearly observed after Fe3O4-NPs exposure. Fe3O4-NPs were ingested and well distributed in the gut, yolk and primary body cavity. Uptake kinetics data showed that the maximum Fe3O4-NPs content (16.4 mg/g) was reached at 30 h. The combined results so far indicate that Fe3O4-NPs have the potential to affect aquatic organisms when released into the marine ecosystems.

Potential role of tracing stem cell transplantation and effects on the immune cell function of ferumoxytol combining with heparin and protamine in vivo/in vitro.

Cell labeling and tracing have played an increasingly important role in the field of stem cell transplantation. Nanocomplexes combining three Food and Drug Administration (FDA)-approved drugs: heparin (H), protamine (P), and ferumoxytol (F) (HPF nanocomplexes) display high labeling efficiency in human adipose tissue-derived stem cells (hADSCs), but their biological safety has not been determined. In this study, we tested the labeling efficiency of HPF in hADSCs through in vitro cytotoxicity studies and in vivo murine preclinical studies using HPF-labeled hADSCs. The labeling process did not cause cell apoptosis and had little effect on cell proliferation. In vivo magnetic resonance imaging (MRI) showed that the HPF-labeled cells produced a hypointense signal that did not affect liver and kidney functions. However, after injection of HPF-labeled cells into mice, lymphocyte transformation testing showed that T and B lymphocyte proliferation was significantly increased. These findings suggest that extensive safety testing of HPF nanocomplexes is necessary; the process to evaluate HPF as an investigative new drug application could therefore be postponed.

Distribution and immunotoxicity by intravenous injection of iron nanoparticles in a murine model.

With the increased application of iron oxide nanoparticles (FeNPs) for biomedical imaging purposes, concerns regarding the onset of the unexpected adverse health effects following exposure have been rapidly raised. In this study, we investigated the tissue distribution and immunotoxicity of FeNPs (2 and 4 mg kg(-1)) over time (2, 4 and 13 weeks) after single intravenous injection. At 13 weeks after a single injection, the iron levels increased in all measured tissues compared to the control, and iron accumulation was notable in the liver, spleen and thymus. These changes were accompanied by changes in levels of redox reaction-related elements, including copper, manganese, zinc and cobalt. In addition, as compared to the control, the number of white blood cells and percentage of neutrophils significantly increased in the treated groups, and the interleukin-8 secretion and lactate dehydrogenase release were clearly elevated in the treated groups along with enhanced expressions of chemotaxis-related proteins. However, expression of antigen presenting related proteins attenuated following accumulation of FeNPs. Taken together, we suggest that FeNPs may primarily induce toxicity in the liver and immune system, and immunotoxicological evaluation should be considered to predict adverse health effects following exposure to NPs.

Assessment of the Phytotoxicity of Metal Oxide Nanoparticles on Two Crop Plants, Maize (Zea mays L.) and Rice (Oryza sativa L.).

In this study, the phytotoxicity of seven metal oxide nanoparticles(NPs)-titanium dioxide (nTiO2), silicon dioxide (nSiO2), cerium dioxide (nCeO2), magnetite (nFe3O4), aluminum oxide (nAl2O3), zinc oxide (nZnO) and copper oxide (nCuO)-was assessed on two agriculturally significant crop plants (maize and rice). The results showed that seed germination was not affected by any of the seven metal oxide NPs. However, at the concentration of 2000 mg·L(-1), the root elongation was significantly inhibited by nCuO (95.73% for maize and 97.28% for rice), nZnO (50.45% for maize and 66.75% for rice). On the contrary, minor phytotoxicity of nAl2O3 was only observed in maize, and no obvious toxic effects were found in the other four metal oxide NPs. By further study we found that the phytotoxic effects of nZnO, nAl2O3 and nCuO (25 to 2000 mg·L(-)¹) were concentration dependent, and were not caused by the corresponding Cu(2+), Zn(2+) and Al(3+) ions (0.11 mg·L(-)¹, 1.27 mg·L(-)¹ and 0.74 mg·L(-)¹, respectively). Furthermore, ZnO NPs (<50 nm) showed greater toxicity than ZnO microparticles(MPs)(<5 µm) to root elongation of both maize and rice. Overall, this study provided valuable information for the application of engineered NPs in agriculture and the assessment of the potential environmental risks.