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  • Potential impact of inorganic nanoparticles on macronutrient digestion: titanium dioxide nanoparticles slightly reduce lipid digestion under simulated gastrointestinal conditions
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-21
    Qian Li, Ti Li, Chengmei Liu, Glen DeLoid, Georgios Pyrgiotakis, Philip Demokritou, Ruojie Zhang, Hang Xiao, David Julian McClements

    Titanium dioxide (TiO2) particles are used in some food products to alter their optical properties, such as whiteness or brightness. These additives typically contain a population of TiO2 nanoparticles (d < 100 nm), which has led to concern about their potential toxicity. The objective of this study was to examine the impact of TiO2 particles on the gastrointestinal fate of oil-in-water emulsions using a simulated gastrointestinal tract (GIT) that includes mouth, stomach, and small intestine phases. Theoretical predictions suggested that TiO2 nanoparticles might inhibit lipid digestion through two physicochemical mechanisms: (i) a fraction of the lipase adsorbs to TiO2 particle surfaces, thereby reducing the amount available to hydrolyze lipid droplets; (ii) some TiO2 particles adsorb to the surfaces of lipid droplets, thereby reducing the lipid surface area exposed to lipase. The importance of these mechanisms was tested by passing protein-coated lipid droplets (2%, w/w) through the simulated GIT in the absence and presence of TiO2 (0.5%, w/w) nanoparticles (18 nm) and fine particles (167 nm). Changes in particle characteristics (size, organization, and charge) and lipid digestion were then measured. Both TiO2 nanoparticles and fine particles had little impact on the aggregation state and charge of the lipid droplets in the different GIT regions, as well as on the rate and extent of lipid digestion. This suggests that the theoretically predicted impact of particle size on lipid digestion was not seen in practice.

    更新日期:2017-12-15
  • Graphene oxide significantly inhibits cell growth at sublethal concentrations by causing extracellular iron deficiency
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-09
    Qilin Yu, Bing Zhang, Jianrong Li, Tingting Du, Xiao Yi, Mingchun Li, Wei Chen, Pedro J. J. Alvarez

    Graphene oxide (GO)-based materials are increasingly being used in medical materials and consumer products. However, their sublethal effects on biological systems are poorly understood. Here, we report that GO (at 10 to 160 mg/L) induced significant inhibitory effects on the growth of different unicellular organisms, including eukaryotes (i.e. Saccharomyces cerevisiae, Candida albicans, and Komagataella pastoris) and prokaryotes (Pseudomonas fluorescens). Growth inhibition could not be explained by commonly reported cytotoxicity mechanisms such as plasma membrane damage or oxidative stress. Based on transcriptomic analysis and measurement of extra- and intracellular iron concentrations, we show that the inhibitory effect of GO was mainly attributable to iron deficiency caused by binding to the O-functional groups of GO, which sequestered iron and disrupted iron-related physiological and metabolic processes. This inhibitory mechanism was corroborated with supplementary experiments, where adding bathophenanthroline disulfonate—an iron chelating agent—to the culture medium exerted similar inhibition, whereas removing surface O-functional groups of GO decreased iron sequestration and significantly alleviated the inhibitory effect. These findings highlight a potential indirect detrimental effect of nanomaterials (i.e. scavenging of critical nutrients), and encourage research on potential biomedical applications of GO-based materials to sequester iron and enhance treatment of iron-dependent diseases such as cancer and some pathogenic infections.

    更新日期:2017-12-15
  • Distinct toxic interactions of TiO2 nanoparticles with four coexisting organochlorine contaminants on algae
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-07
    Shuai Zhang, Rui Deng, Daohui Lin, Fengchang Wu

    Engineered nanoparticles are increasingly discharged into the environment. After discharge, these nanoparticles can interact with co-existing organic contaminants, resulting in a phenomena referred to as ‘joint toxicity’. This study evaluated joint toxicities of TiO2 nanoparticles (TiO2NPs) with four different (atrazine, hexachlorobenzene, pentachlorobenzene, and 3,3′,4,4′-tetrachlorobiphenyl) organochlorine contaminants (OCs) toward algae (Chlorella pyrenoidosa). The potential mechanisms underlying the joint toxicity were discussed, including TiO2NPs–OC interactions, effects of TiO2NPs and OCs on biophysicochemical properties of algae and effects of TiO2NPs and OCs on each other’s bioaccumulation in algae. The results indicate that coexposure led to a synergistic effect on the joint toxicity for TiO2NPs–atrazine, antagonistic effect for TiO2NPs–hexachlorobenzene and TiO2NPs–3,3',4,4'-tetrachlorobiphenyl, and an additive effect for TiO2NPs–pentachlorobenzene. There was nearly no adsorption of OCs by TiO2NPs, and the physicochemical properties of TiO2NPs were largely unaltered by the presence of OCs. However, both OCs and NPs affected the biophysicochemical properties of algal cells and thereby influenced the cell surface binding and/or internalization. TiO2NPs significantly increased the bioaccumulation of each OC. However, with the exception of atrazine, the bioaccumulation of TiO2NPs decreased when used with each OC. The distinct joint toxicity outcomes were a result of the balance between the increased toxicities of OCs (increased bioaccumulations) and the altered toxicity of TiO2NPs (bioaccumulation can either increase or decrease). These results can significantly improve our understanding of the potential environmental risks associated with NPs.

    更新日期:2017-12-15
  • Comparison of acute to chronic ratios between silver and gold nanoparticles, using Ceriodaphnia dubia
    Nanotoxicology (IF 6.428) Pub Date : 2017-12-01
    Ashley R. Harmon, Alan J. Kennedy, Jennifer G. Laird, Anthony J. Bednar, Jeffery A. Steevens

    As integration of nanoparticles (NPs) into products becomes more common, the need to address the paucity of chronic hazard information for aquatic environments required to determine risk potential increases. This study generated acute and chronic toxicity reference values for Ceriodaphnia dubia exposed to 20 and 100 nm silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) to generate and evaluate potential differences in acute-to-chronic ratios (ACR) using two different feeding methods. A modified feeding procedure was employed alongside the standard procedures to investigate the influence of food on organism exposure. An 8-h period before food was added allowed direct organism exposure to NP dispersions (and associated ions) without food-to-NP interactions. The AgNPs [chronic lethal median concentrations (LC50) between 18.7 and 31.9 µg/L] were substantially more toxic than AuNPs (LC50 = 21 507 to >26 384 µg/L). The modified chronic testing method resulted in greater sensitivity in AgNPs exposures. However, the modified feeding ration had less of an effect in exposures to the larger (100 nm) AgNPs compared to smaller particles (20 nm). The ACRs for AgNPs using the standard feeding ration were 1.6 and 3.5 for 20 nm and 100 nm, respectively. The ACRs for AgNPs using the modified feeding ration were 3.4 and 7.6 for 20 nm and 100 nm NPs, respectively. This supports that the addition of the standard feeding ration decreases C. dubia chronic sensitivity to AgNPs, although it must also be recognized organisms may be sensitized due to less access to food. The ACRs for 20 nm and 100 nm AuNPs (standard ration only) were 4.0 and 3.0, respectively. It is important to also consider that dissolved Ag+ ions are more toxic than AgNPs, based on both acute toxicity values in the cited literature and chronic toxicity thresholds generated in this study that support existing thresholds that Ag+ are likely protective of AgNPs effects.

    更新日期:2017-12-15
  • Impact of TiO2 and ZnO nanoparticles on an aquatic microbial community: effect at environmentally relevant concentrations
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-10
    Nathalia Londono, Ariel R. Donovan, Honglan Shi, Matthew Geisler, Yanna Liang

    To investigate effects of engineered nanoparticles (ENPs) at environmentally relevant concentrations to aquatic microbial communities, TiO2 at 700 µg/L and ZnO at 70 µg/L were spiked to river water samples either separately or combined. Compared to controls where no ENPs were added, the addition of TiO2 ENPs alone at the tested concentration had no statistically significant effect on both the bacterial and eukaryotic communities. The presence of added ENPs: ZnO or ZnO + TiO2 led to significant shift of the microbial community structure and genus distribution. This shift was more obvious for the bacteria than the eukaryotes. Based on results from single particle – inductively coupled plasma – mass spectrometry (SP-ICP-MS), all ENPs aggregated rapidly in water and resulted in much larger particles sizes than the original counterparts. “Dissolved” (including particles smaller than the size detection limits and dissolved ions) concentrations of Ti and Zn increased, too in treatment groups vs. the controls.

    更新日期:2017-12-15
  • Bacterial endotoxin (lipopolysaccharide) binds to the surface of gold nanoparticles, interferes with biocorona formation and induces human monocyte inflammatory activation
    Nanotoxicology (IF 6.428) Pub Date : 2017-12-01
    Yang Li, Zhenzhen Shi, Isabella Radauer-Preiml, Ancuela Andosch, Eudald Casals, Ursula Luetz-Meindl, Macarena Cobaleda, Zhoumeng Lin, Majid Jaberi-Douraki, Paola Italiani, Jutta Horejs-Hoeck, Martin Himly, Nancy A. Monteiro-Riviere, Albert Duschl, Victor F. Puntes, Diana Boraschi

    Nanoparticles (NPs) are easily contaminated by bacterial endotoxin (lipopolysaccharide [LPS]). The presence of LPS can be responsible for many immune/inflammatory effects attributed to NPs. In this study, we examined the effects of LPS adsorption on the NP surface on the formation of a biocorona in biological fluids and on the subsequent inflammation-inducing activity of NPs. Different gold (Au) NPs with sizes ranging from 10 to 80 nm and with different surface functionalization (sodium citrate, lipoic acid, and branched polyethyleneimine (BPEI), or polyethylene glycol (PEG)) were exposed to E. coli LPS under different conditions. The binding capacity of LPS to the surface of AuNPs was dose- and time-dependent. LPS attached to sodium citrate and lipoic acid coatings, but did not adhere to BPEI- or PEG-coated NPs. By computational simulation, the binding of LPS to AuNPs seems to follow the Langmuir absorption isotherm. The presence of LPS on AuNP surface interfered and caused a decrease in the formation of the expected biomolecular corona upon incubation in human plasma. LPS-coated AuNPs, but not the LPS-free NPs, induced significant inflammatory responses in vitro. Notably, while free LPS did also induce an anti-inflammatory response, LPS bound to NPs appeared unable to do so. In conclusion, the unintentional adsorption of LPS onto the NP surface can affect the biocorona formation and the inflammatory properties of NPs. Thus, for an accurate interpretation of NP interactions with cells, it is extremely important to be able to distinguish the intrinsic NP biological effects from those caused by biologically active contaminants such as endotoxin.

    更新日期:2017-12-15
  • Amorphous silica nanoparticles induce malignant transformation and tumorigenesis of human lung epithelial cells via P53 signaling
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-22
    Caixia Guo, Ji Wang, Man Yang, Yang Li, Shuxiang Cui, Xianqing Zhou, Yanbo Li, Zhiwei Sun

    Rapid development and deployment of engineered nanomaterials, such as amorphous silica nanoparticles (SiNPs) in various commercial and biomedical applications have raised concerns about their potential adverse health effects, especially their chronic effects which have not been well addressed. In this study, human lung epithelial cells, BEAS-2B were continuously exposed to amorphous SiNPs, 5 μg/mL for 40 passages. We demonstrated here that prolonged exposure of BEAS-2B cells to amorphous SiNPs induced malignant transformation as indicated by enhanced cellular proliferation, anchorage-independent cell growth, and increased cell migration. The transformed cells induced tumorigenesis in nude mice. Furthermore, a comprehensive understanding of genome-wide transcriptional analysis was performed to clarify the molecular mechanisms based on microarray and bioinformatics analysis. Microarray data analysis demonstrated that chronic exposure of SiNPs affected expression of 821 genes, including 5 up-regulated and 816 down-regulated genes. Gene ontology and pathway analysis showed that SiNPs caused significant changes in gene expression patterns related to many important functions and pathways, mainly including response to cellular processes, oxidative stress, DNA damage, and cancer. In addition, Signal-net analysis indicated the most prominent significant role of tumor protein p53 in amorphous SiNPs-induced transformation. Further, data confirmed the inactivated p53 and aberrant p53 signaling under chronic amorphous SiNPs exposure. In summary, our data firstly demonstrated chronically low-dose amorphous SiNPs exposure resulted in malignant transformation of human lung epithelial cell via p53 signaling, which provides new in vitro evidence for the carcinogenicity of amorphous SiNPs.

    更新日期:2017-12-15
  • Changes in DNA methylation induced by multi-walled carbon nanotube exposure in the workplace
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-30
    Manosij Ghosh, Deniz Öner, Katrien Poels, Ali M. Tabish, Jelle Vlaanderen, Anjoeka Pronk, Eelco Kuijpers, Qing Lan, Roel Vermeulen, Bram Bekaert, Peter HM Hoet, Lode Godderis

    This study was designed to assess the epigenetic alterations in blood cells, induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The study population comprised of MWCNT-exposed workers (n=24) and unexposed controls (n=43) from the same workplace. We measured global DNA methylation/hydroxymethylation levels on the 5th cytosine residues using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. Sequence-specific methylation of LINE1 retrotransposable element 1 (L1RE1) elements, and promoter regions of functionally important genes associated with epigenetic regulation [DNA methyltransferase-1 (DNMT1) and histone deacetylase 4 (HDAC4)], DNA damage/repair and cell cycle pathways [nuclear protein, coactivator of histone transcription/ATM serine/threonine kinase (NPAT/ATM)], and a potential transforming growth factor beta (TGF-β) repressor [SKI proto-oncogene (SKI)] were studied using bisulfite pyrosequencing. Analysis of global DNA methylation levels and hydroxymethylation did not reveal significant difference between the MWCNT-exposed and control groups. No significant changes in Cytosine-phosphate-Guanine (CpG) site methylation were observed for the LINE1 (L1RE1) elements. Further analysis of gene-specific DNA methylation showed a significant change in methylation for DNMT1, ATM, SKI, and HDAC4 promoter CpGs in MWCNT-exposed workers. Since DNA methylation plays an important role in silencing/regulation of the genes, and many of these genes have been associated with occupational and smoking-induced diseases and cancer (risk), aberrant methylation of these genes might have a potential effect in MWCNT-exposed workers.

    更新日期:2017-12-15
  • Metal load assessment in patient pulmonary lavages: towards a comprehensive mineralogical analysis including the nano-sized fraction
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-25
    Valérie Forest, Jean-Michel Vergnon, Cyril Guibert, Dimitrios Bitounis, Lara Leclerc, Gwendoline Sarry, Jérémie Pourchez

    Mineralogical analyses of clinical samples have been proved useful to identify causal relationship between exposure to airborne particles and pulmonary diseases. The most striking example is asbestosis where the assessment of asbestos bodies in patient lung samples has allowed defining values specific of pathologies. However, this type of analyses only considers the micro-sized fraction of the particles, neglecting the specific impact of nano-sized particles which have been otherwise shown to be reactive and able to induce biological effects. Similarly, in nanotoxicology, the mineralogical analysis of pulmonary fluids could be used as an indicator of exposure to inhaled nanoparticles and could help investigations on the relationship between exposure to these nanoparticles and lung diseases. We designed this study first to demonstrate the technical feasibility of this approach, then to get a clear picture of the metals present, and in what form, in patient lungs and finally to determine if indeed it is worth investigating separately the micro, sub-micro and nano fractions. Broncho-alveolar lavages were recovered from 100 patients suffering from interstitial lung diseases. A protocol was specifically developed to isolate three fractions containing respectively microparticles, sub-microparticles and nanoparticles with ions. The metal content in each fraction was qualitatively and quantitatively characterized. Results showed significant differences between the three fractions in terms of metal load confirming that the separate analysis of the fractions is relevant. It also means that the assessment of the micro-sized fraction alone, as commonly done in clinical practice, only gives a partial view of the mineralogical analysis.

    更新日期:2017-12-15
  • The elemental changes occurring in the rat liver after exposure to PEG-coated iron oxide nanoparticles: total reflection x-ray fluorescence (TXRF) spectroscopy study
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-29
    Katarzyna Matusiak, Agnieszka Skoczen, Zuzanna Setkowicz, Aldona Kubala-Kukus, Ilona Stabrawa, Małgorzata Ciarach, Krzysztof Janeczko, Aleksandra Jung, Joanna Chwiej

    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.

    更新日期:2017-12-15
  • Assessment of evidence for nanosized titanium dioxide-generated DNA strand breaks and oxidatively damaged DNA in cells and animal models
    Nanotoxicology (IF 6.428) Pub Date : 2017-11-27
    Peter Møller, Ditte Marie Jensen, Regitze Sølling Wils, Maria Helena Guerra Andersen, Pernille Høgh Danielsen, Martin Roursgaard

    Nanosized titanium dioxide (TiO2) has been investigated in numerous studies on genotoxicity, including comet assay endpoints and oxidatively damaged DNA in cell cultures and animal models. The results have been surprisingly mixed, which might be attributed to physico-chemical differences of the tested TiO2. In the present review, we assess the role of certain methodological issues and publication bias. The analysis shows that studies on DNA strand breaks without proper assay controls or very low intra-group variation tend to show statistically significant effects. Levels of oxidatively damaged DNA, measured by the enzyme-modified comet assay, tend to show no effect in studies that have not included proper assay controls or they have uncertainty about the measurement. In addition, there are indications of publication and reporting bias. Nevertheless, the analysis shows that Aeroxide P25 generates DNA strand breaks in a concentration-dependent manner, which is not dependent on the duration of exposure. The standard comet assay seems to be able to discriminate between the genotoxicity of different types of TiO2, where anatase TiO2 seems to be the form with strongest genotoxic potential. Cell culture studies also demonstrate increased levels of oxidatively damaged DNA after exposure to TiO2. There are relatively few studies on animal models where DNA strand breaks and oxidatively damaged DNA have been tested with reliable methods. Collectively, this review shows that exposure to nanosized TiO2 is associated with genotoxicity in cells, whereas there are still too few reliable studies to assess the genotoxic potential in animal models.

    更新日期:2017-12-15
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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