Shape-Related Toxicity of Titanium Dioxide Nanofibres

Titanium dioxide (TiO₂) nanofibres are a novel fibrous nanomaterial with increasing applications in a variety of fields. While the biological effects of TiO₂ nanoparticles have been extensively studied, the toxicological characterization of TiO₂ nanofibres is far from being complete. In this study, we evaluated the toxicity of commercially available anatase TiO₂ nanofibres using TiO₂ nanoparticles (NP) and crocidolite asbestos as non-fibrous or fibrous benchmark materials. The evaluated endpoints were cell viability, haemolysis, macrophage activation, trans-epithelial electrical resistance (an indicator of the epithelial barrier competence), ROS production and oxidative stress as well as the morphology of exposed cells. The results showed that TiO₂ nanofibres caused a cell-specific, dose-dependent decrease of cell viability, with larger effects on alveolar epithelial cells than on macrophages. The observed effects were comparable to those of crocidolite, while TiO₂ NP did not decrease cell viability. TiO₂ nanofibres were also found endowed with a marked haemolytic activity, at levels significantly higher than those observed with TiO₂ nanoparticles or crocidolite. Moreover, TiO₂ nanofibres and crocidolite, but not TiO₂ nanoparticles, caused a significant decrease of the trans-epithelial electrical resistance of airway cell monolayers. SEM images demonstrated that the interaction with nanofibres and crocidolite caused cell shape perturbation with the longest fibres incompletely or not phagocytosed. The expression of several pro-inflammatory markers, such as NO production and the induction of Nos2 and Ptgs2, was significantly increased by TiO₂ nanofibres, as well as by TiO₂ nanoparticles and crocidolite. This study indicates that TiO₂ nanofibres had significant toxic effects and, for most endpoints with the exception of pro-inflammatory changes, are more bio-active than TiO₂ nanoparticles, showing the relevance of shape in determining the toxicity of nanomaterials. Given that several toxic effects of TiO₂ nanofibres appear comparable to those observed with crocidolite, the possibility that they exert length dependent toxicity in vivo seems worthy of further investigation.     

Titanium Dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells

Nanomaterials are used in diverse fields including food, cosmetic, and medical industries. Titanium dioxide nanoparticles (TiO₂-NP) are widely used, but their effects on biological systems and mechanism of toxicity have not been elucidated fully. Here, we report the toxicological mechanism of TiO₂-NP in cell organelles. Human bronchial epithelial cells (16HBE14o-) were exposed to 50 and 100 μg/mL TiO₂-NP for 24 and 48 h. Our results showed that TiO₂-NP induced endoplasmic reticulum (ER) stress in the cells and disrupted the mitochondria-associated endoplasmic reticulum membranes (MAMs) and calcium ion balance, thereby increasing autophagy. In contrast, an inhibitor of ER stress, tauroursodeoxycholic acid (TUDCA), mitigated the cellular toxic response, suggesting that TiO₂-NP promoted toxicity via ER stress. This novel mechanism of TiO₂-NP toxicity in human bronchial epithelial cells suggests that further exhaustive research on the harmful effects of these nanoparticles in relevant organisms is needed for their safe application.     

Synthesis of Black TiOx Nanoparticles by Mg Reduction of TiO2 Nanocrystals and their Application for Solar Water Evaporation

TiO_x (x < 2) nanoparticles with tunable colors from white to gray to blue–gray to black are synthesized by magnesium (Mg) reduction of white P25 TiO₂ nanocrystals followed by removal of excess Mg with aqueous HCl and distilled water. Increasing amounts of Mg smoothly decrease the oxygen content in TiO_x which is responsible for the gradual increase in light absorption and concomitant darkening of its color from white to black with decreasing values of x. The as‐synthesized TiO_x nanoparticles are spin‐coated onto the surface of a stainless steel mesh followed by surface superhydrophobization in order to test their performance as a solar water evaporator. Results from the tests show that the black TiO_x efficiently generates water vapor with a solar thermal conversion efficiency as high as 50% under solar‐simulated light irradiance at an intensity of 1000 W m^–2 (1 Sun). Moreover, TiO_x nanoparticles have inherent advantages over other materials used for solar water desalination, such as their tunable light absorption, low‐cost, low‐toxicity, superhydrophobicity, and chemical stability.     

Toxicity of commercially available engineered nanoparticles to Caco-2 and SW480 human intestinal epithelial cells

The effects of ingestion of engineered nanoparticles (NPs), especially via drinking water, are unknown. Using NPs spiked into synthetic water and cell culture media, we investigated cell death, oxidative stress, and inflammatory effects of silver (Ag), titanium dioxide (TiO₂), and zinc oxide (ZnO) NPs on human intestinal Caco-2 and SW480 cells. ZnO NPs were cytotoxic to both cell lines, while Ag and TiO₂ NPs were toxic only at 100 mg/L to Caco-2 and SW480, respectively. ZnO NPs led to significant cell death in synthetic freshwaters with 1 % phosphate-buffered saline in both cell lines, while Ag and TiO₂ NPs in buffered water led to cell death in SW480 cells. NP exposures did not yield significant increased reactive oxygen species generation but all NP exposures led to increased IL-8 cytokine generation in both cell lines. These results indicate cell stress and cell death from NP exposures, with a varied response based on NP composition.     

Two Channels of Charge Generation in Perylene Monoimide Solid‐State Dye‐Sensitized Solar Cells

The mechanism of charge generation in solid‐state dye‐sensitized solar cells using triarylamine‐substituted perylene monoimide dyes is studied by vis‐NIR broadband pump‐probe transient absorption spectroscopy. The experiments demonstrate that photoinduced electron injection into the TiO₂ can only occur in regions where Li⁺, from the commonly used Li‐TFSI additive salt, is present on the TiO₂ surface. Incomplete surface coverage by Li⁺ means that some dye excitons cannot inject their electron into the TiO₂. However it is observed in the solar cell structure that some of the dye excitons that cannot directly inject an electron still contribute to free charge generation by the previously hypothesized reductive quenching mechanism (hole transfer to the solid‐state hole transporter followed by electron injection from the dye anion into the TiO₂). The contribution of reductive quenching to the quantum efficiency of charge generation is significant, raising it from 68% to over 80%. Optimization of this reductive quenching pathway could be exploited to maintain high quantum efficiency in dyes with greater NIR absorption to achieve overall enhancements in device performance. It is demonstrated that broadband NIR transient spectroscopy is necessary to obtain population kinetics in these systems, as strong Stark effects distort the population kinetics in the visible region.     

Metabolic effects of TiO2 nanoparticles,a common component of sunscreens and cosmetics,on human keratinocytes

The long-term health risks of nanoparticles remain poorly understood, which is a serious concern given their prevalence in the environment from increased industrial and domestic use. The extent to which such compounds contribute to cellular toxicity is unclear, and although it is known that induction of oxidative stress pathways is associated with this process, the proteins and the metabolic pathways involved with nanoparticle-mediated oxidative stress and toxicity are largely unknown. To investigate this problem further, the effect of TiO₂ on the HaCaT human keratinocyte cell line was examined. The data show that although TiO₂ does not affect cell cycle phase distribution, nor cell death, these nanoparticles have a considerable and rapid effect on mitochondrial function. Metabolic analysis was performed to identify 268 metabolites of the specific pathways involved and 85 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. Importantly, the uptake of nanoparticles into the cultured cells was restricted to phagosomes, TiO₂ nanoparticles did not enter into the nucleus or any other cytoplasmic organelle. No other morphological changes were detected after 24-h exposure consistent with a specific role of mitochondria in this response.     

Role of glycolysis and antioxidant enzymes in the toxicity of amyloid beta peptide Aβ<Subscript>25–35</Subscript> to erythrocytes

The role of glycolysis and antioxidant enzymes in amyloid beta peptide Aβ_25–35 toxicity to human and rat erythrocytes was studied. The erythrotoxicity of Aβ_25–35 was shown to increase two-to fourfold both in the absence of glucose in the incubation medium and upon the addition of sodium fluoride, an enolase inhibitor. Potassium cyanide, a Cu,Zn-superoxide dismutase inhibitor, abolishes the toxic effect of Aβ_25–35 to erythrocytes, whereas mercaptosuccinate, a glutathione peroxidase inhibitor, and ouabain, a Na⁺,K⁺-ATPase inhibitor, promote it. Sodium azide, a catalase inhibitor, did not affect the cell lysis under the action of Aβ_25–35. The results support the hypothesis that H₂O₂, Cu,Zn superoxide dismutase, and glutathione peroxidase are involved in the toxicity mechanism rather than superoxide radical. Glycolysis and Na⁺,K⁺-ATPase play a substantial protective role. Fullerene C₆₀ nanoparticles are toxic to erythrocytes of both types; their toxicity is not related to enhanced oxidative stress and the mechanism of toxicity differs from that of Aβ_25–35.     

Redox Targeting of Anatase TiO2 for Redox Flow Lithium‐Ion Batteries

Anatase TiO₂ is an extensively studied anode material for lithium‐ion batteries because of its superior capability of storing Li⁺ electrochemically. Here reversible lithium storage of TiO₂ is achieved chemically using redox targeting reactions. In the presence of a pair of redox mediators, bis(pentamethylcyclopentadienyl)cobalt (CoCp^* ₂) and cobaltocene (CoCp₂) in an electrolyte, TiO₂ and its lithiated form Li _x TiO₂ can be reduced and oxidized by CoCp^* ₂ and CoCp₂ ⁺, respectively, which accompany Li⁺ insertion and extraction, albeit without attaching the TiO₂ onto the electrode. The reversible chemical lithiation/delithiation and the involved phase transitions are unambiguously confirmed using density functional theory (DFT) calculations, UV‐vis spectroscopy, X‐ray photoelectron spectoscopy (XPS), and Raman spectroscopy. A redox flow lithium‐ion battery (RFLB) half‐cell is assembled and evaluated, which is a critical step towards the development of RFLB full cells.     

Neurotoxicity mediated by oxidative stress caused by titanium dioxide nanoparticles in human neuroblastoma (SH-SY5Y) cells

BackgroundTitanium is widely used in biomedicine. Due to biotribocorrosion, titanium dioxide (TiO₂) nanoparticles (NPs) can be released from the titanium implant surface, enter the systemic circulation, and migrate to various organs and tissues including the brain. A previous study showed that 5 nm TiO₂ NPs reached the highest concentration in the brain. Even though TiO₂ NPs are believed to possess low toxicity, little is known about their neurotoxic effects. The aim of the study was to evaluate in vitro the effects of 5 nm TiO₂ NPs on a human neuroblastoma (SH-SY5Y) cell line.MethodsCell cultures were divided into non-exposed and exposed to TiO₂ NPs for 24 h. The following were evaluated: reactive oxygen species (ROS) generation, apoptosis, cellular antioxidant response, endoplasmic reticulum stress and autophagy.ResultsExposure to TiO₂ NPs induced ROS generation in a dose dependent manner, with values reaching up to 10 fold those of controls (p < 0.001). Nrf2 nuclear localization and autophagy, also increased in a dose dependent manner. Apoptosis increased by 4- to 10-fold compared to the control group, depending on the dose employed.ConclusionsOur results show that TiO₂ NPs cause ROS increase, induction of ER stress, Nrf2 cytoplasmic translocation to the nucleus and apoptosis. Thus, neuroblastoma cell response to TiO₂ NPs may be associated with an imbalance of the oxidative metabolism where endoplasmic reticulum-mediated signal pathway seems to be the main neurotoxic mechanism.     

Ultrafine MoO2‐Carbon Microstructures Enable Ultralong‐Life Power‐Type Sodium Ion Storage by Enhanced Pseudocapacitance

The achievement of the superior rate capability and cycling stability is always the pursuit of sodium‐ion batteries (SIBs). However, it is mainly restricted by the sluggish reaction kinetics and large volume change of SIBs during the discharge/charge process. This study reports a facile and scalable strategy to fabricate hierarchical architectures where TiO₂ nanotube clusters are coated with the composites of ultrafine MoO₂ nanoparticles embedded in carbon matrix (TiO₂@MoO₂‐C), and demonstrates the superior electrochemical performance as the anode material for SIBs. The ultrafine MoO₂ nanoparticles and the unique nanorod structure of TiO₂@MoO₂‐C help to decrease the Na⁺ diffusion length and to accommodate the accompanying volume expansion. The good integration of MoO₂ nanoparticles into carbon matrix and the cable core role of TiO₂ nanotube clusters enable the rapid electron transfer during discharge/charge process. Benefiting from these structure merits, the as‐made TiO₂@MoO₂‐C can deliver an excellent cycling stability up to 10 000 cycles even at a high current density of 10 A g^?1. Additionally, it exhibits superior rate capacities of 110 and 76 mA h g^?1 at high current densities of 10 and 20 A g^?1, respectively, which is mainly attributed to the high capacitance contribution.     

The cytotoxic targets of anatase or rutile + anatase nanoparticles depend on the plant species

The potential toxicity of nanoparticles (NPs) is under debate. Information about TiO₂ NPs phytotoxicity is still limited partly due to the different TiO₂ NP forms that may be found in the environment. The present work investigated the impact of different TiO₂ NPs forms (rutile and anatase) on germination, growth, cell cycle profile, ploidy level, and micronucleus formation in Lactuca sativa (lettuce) and Ocimum basilicum (basil). Seeds were exposed to anatase (ana) or rutile + anatase (rut+ana) at concentrations 5 - 150 mg dm^-3 for 5 d and after that different parameters were analyzed. Rut+ana showed high potential to impair germination and growth. On the other hand, ana alone showed a positive influence on seedling growth. Despite that, ana induced severe alterations in cell cycle dynamics. Regarding species, basil was more sensitive to TiO₂ NPs cytostatic effects (delay/arrest in G₀/G₁ phase), whereas in lettuce, TiO₂ NPs were more genotoxic (micronucleus formation increase). Finally, we propose that, besides germination and plant growth, cell cycle dynamics and micronucleus formation can be sensitive biomarkers of these NPs.     

Protective effect of binaphthyl diselenide,a synthetic organoselenium compound,on 2‐nitropropane‐induced hepatotoxicity in rats

Organoselenides have been documented as promising pharmacological agents against a number of diseases associated with oxidative stress. Here we have investigated, for the first time, the potential antioxidant activity of binaphthyl diselenide ((NapSe)₂; 50 mg kg^?1, p.o.) against the 2‐nitropropane (2‐NP)‐induced hepatoxicity in rats, using different end points of toxicity (liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatinine). In addition, in view of the association of oxidative stress with 2‐NP exposure, hepatic lipid peroxidation, ascorbic acid levels, δ‐aminolevulinate dehydratase (δ‐ALA‐D) and catalase (CAT) activities were evaluated. 2‐NP caused an increase of AST, ALT and hepatic lipid peroxidation. 2‐NP also caused hepatic histopathological alterations and δ‐ALA‐D inhibition. (NapSe)₂ (50 mg kg^?1) prevented 2‐NP‐induced changes in plasmatic ALT and AST activities and also prevented changes in hepatic histology, δ‐ALA‐D and lipid peroxidation. Results presented here indicate that the protective mechanism of (NapSe)₂ against 2‐NP hepatotoxicity is possibly linked to its antioxidant activity. Copyright © 2010 John Wiley & Sons, Ltd.     

A laser ablation technique maps differences in elemental composition in roots of two barley cultivars subjected to salinity stress

In saline soils, high levels of sodium (Na⁺) and chloride (Cl^?) ions reduce root growth by inhibiting cell division and elongation, thereby impacting on crop yield. Soil salinity can lead to Na⁺ toxicity of plant cells, influencing the uptake and retention of other important ions [i.e. potassium (K⁺)] required for growth. However, measuring and quantifying soluble ions in their native, cellular environment is inherently difficult. Technologies that allow in situ profiling of plant tissues are fundamental for our understanding of abiotic stress responses and the development of tolerant crops. Here, we employ laser ablation‐inductively coupled plasma‐mass spectrometry (LA‐ICP‐MS) to quantify Na, K and other elements [calcium (Ca), magnesium (Mg), sulphur (S), phosphorus (P), iron (Fe)] at high spatial resolution in the root growth zone of two genotypes of barley (Hordeum vulgare) that differ in salt‐tolerance, cv. Clipper (tolerant) and Sahara (sensitive). The data show that Na⁺ was excluded from the meristem and cell division zone, indicating that Na⁺ toxicity is not directly reducing cell division in the salt‐sensitive genotype, Sahara. Interestingly, in both genotypes, K⁺ was strongly correlated with Na⁺ concentration, in response to salt stress. In addition, we also show important genetic differences and salt‐specific changes in elemental composition in the root growth zone. These results show that LA‐ICP‐MS can be used for fine mapping of soluble ions (i.e. Na⁺ and K⁺) in plant tissues, providing insight into the link between Na⁺ toxicity and root growth responses to salt stress.     

Organ-specific effects of the auxin herbicide 2,4-D on the oxidative stress and senescence-related parameters of the stems of pea plants

Oxidative stress and senescence have been shown to participate in the toxicity mechanism of auxin herbicides in the leaves and roots of sensitive plants. However, their role in stem toxicity has not been studied yet. In this work, we report the effect of foliar or root applications of the auxin herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the parameters of oxidative stress and senescence of stems of pea (Pisum sativum L.) plants. Contrary to their effect on the pea leaves, in the stems 2,4-D applications did not cause oxidative stress, as shown by the parameters of lipid peroxidation, protein carbonyls, and total and protein thiols. Moreover, they inhibited the superoxide radical (O₂^.−)-producing xanthine oxidase (XOD) activity and stimulated the antioxidant activities of catalase (CAT), guaiacol peroxidase (GPOX), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione S-transferase (GST) and Krebs cycle NAD⁺-isocitrate dehydrogenase (IDH). Applications of 2,4-D also did not induce senescence in the pea stems, as shown by the increase of proteins, the lack of stimulation of proteolytic activity, and the inhibition of senescence-related isocitrate lyase (ICL) activity. However, they stimulated the H₂O₂-producing acyl-CoA oxidase (ACOX) activity of fatty acid beta oxidation. Results suggest that oxidative stress and senescence are not involved in the mechanism of toxicity of 2,4-D in the stems of pea plants, and that these phenomena are not whole-plant toxicity mechanisms for auxin herbicides in susceptible plants. Results also suggest that the effect of 2,4-D on the oxidative metabolism of pea plants might be organ-specific.     

Changes in the C/N balance caused by increasing external ammonium concentrations are driven by carbon and energy availabilities during ammonium nutrition in pea plants: the key roles of asparagine synthetase and anaplerotic enzymes

An understanding of the mechanisms underlying ammonium (NH₄⁺) toxicity in plants requires prior knowledge of the metabolic uses for nitrogen (N) and carbon (C). We have recently shown that pea plants grown at high NH₄⁺ concentrations suffer an energy deficiency associated with a disruption of ionic homeostasis. Furthermore, these plants are unable to adequately regulate internal NH₄⁺ levels and the cell‐charge balance associated with cation uptake. Herein we show a role for an extra‐C application in the regulation of C–N metabolism in NH₄⁺‐fed plants. Thus, pea plants (Pisum sativum) were grown at a range of NH₄⁺ concentrations as sole N source, and two light intensities were applied to vary the C supply to the plants. Control plants grown at high NH₄⁺ concentration triggered a toxicity response with the characteristic pattern of C‐starvation conditions. This toxicity response resulted in the redistribution of N from amino acids, mostly asparagine, and lower C/N ratios. The C/N imbalance at high NH₄⁺ concentration under control conditions induced a strong activation of root C metabolism and the upregulation of anaplerotic enzymes to provide C intermediates for the tricarboxylic acid cycle. A high light intensity partially reverted these C‐starvation symptoms by providing higher C availability to the plants. The extra‐C contributed to a lower C4/C5 amino acid ratio while maintaining the relative contents of some minor amino acids involved in key pathways regulating the C/N status of the plants unchanged. C availability can therefore be considered to be a determinant factor in the tolerance/sensitivity mechanisms to NH₄⁺ nutrition in plants.     

内质网在纳米材料毒性效应形成中的作用及机制

随着纳米材料在食品、药物、生物医学等多领域的应用,其在生产使用过程中对人类健康的影响引起了广泛关注.内质网是蛋白质折叠与加工修饰、脂质合成以及Ca~(2+)储存的主要场所,是维护细胞内稳态的重要细胞器.内质网作为纳米材料的主要靶细胞器之一,在纳米材料引起的毒性效应中起重要作用.本文结合近年来国内外相关研究进展,阐述了纳米银(Ag-NPs)、纳米金(Au-NPs)、纳米二氧化钛(TiO_2-NPs)、纳米氧化锌(ZnO-NPs)、纳米二氧化硅(SiO_2-NPs)、富勒烯(C_(60))、单壁与多壁碳纳米管(SWCNTs/MWCNTs)以及石墨烯与氧化石墨烯(GO)等典型纳米材料对内质网结构与功能的影响,并归纳总结了内质网在不同纳米材料诱导的毒性效应中的作用及其异同点.纳米材料可通过引起内质网应激诱导细胞凋亡、炎症反应以及细胞自噬,还可通过激活IP_3信号通路诱导内质网Ca~(2+)释放激活钙依赖的细胞凋亡.纳米材料可在内质网中积累造成结构损伤及功能障碍,还可诱导内质网自噬.     

Toxicity and cellular responses of intestinal cells exposed to titanium dioxide

The increasing use of nanomaterials in healthcare and industrial products heightens the possibility of their ingestion by humans, other mammals, and fish. While toxicity of many nanomaterials has recently been studied, reports of non-lethal effects of nanomaterials remain ill-defined. This study investigates possible pathways by which nanoparticles, titanium dioxide (TiO₂), could cross the epithelium layer by employing both toxicity and mechanistic studies. This study provides evidence that at 10 μg/mL and above, TiO₂ nanoparticles cross the epithelial lining of the intestinal model by transcytosis, albeit at low levels. TiO₂ was able to penetrate into and through the cells without disrupting junctional complexes, as measured by γ-catenin. To monitor the epithelial integrity, transepithelial electrical resistance (TEER) was employed and determined low concentrations (10 or 100 μg/mL) of TiO₂ do not disrupt epithelial integrity. Live/dead analysis results did not show cell death after exposure to TiO₂. In addition, at 10 μg/mL (and above) TiO₂ nanoparticles begin alteration of both microvillar organization on the apical surface of the epithelium as well as induce a rise in intracellular-free calcium. The latter is a mechanism cells use to respond to extracellular stimuli and may be linked to the alteration of the apical microvilli. Although TiO₂ does not show cell death, the implication of other, non-lethal, effects could lead to undesired outcomes (i.e., disease, malnutrition, shortened life span, etc.).     

Titanium nanoparticles influence the Akt/Tor signal pathway in the silkworm,Bombyx mori,silk gland

Various nanoparticles, such as silver nanoparticles (AgNPs) and titanium nanoparticles (TiO₂NPs) are increasingly used in industrial processes. Because they are released into the environment, research into their influence on the biosphere is necessary. Among its other effects, dietary TiO₂NPs promotes silk protein synthesis in silkworms, which prompted our hypothesis that TiO₂NPs influence protein kinase B (Akt)/Target of rapamycin (Tor) signaling pathway (Akt/Tor) signaling in their silk glands. The Akt/Tor signaling pathway is a principle connector integrating cellular reactions to growth factors, metabolites, nutrients, protein synthesis, and stress. We tested our hypothesis by determining the influence of dietary TiO₂NPs (for 72 h) and, separately, of two Akt/Tor pathway inhibitors (LY294002 and rapamycin) on expression of Akt/Tor signaling pathway genes and proteins in the silk glands. TiO₂NPs treatments led to increased accumulation of mRNAs for Akt, Tor1 and Tor2 by 1.6‐, 12.1‐, and 4.8‐fold. Dietary inhibitors led to 2.6‐ to 4‐fold increases in mRNAs encoding Akt and substantial decreases in mRNAs encoding Tor1 and Tor2. Western blot analysis showed that dietary TiO₂NPs increased the phosphorylation of Akt and its downstream proteins. LY294002 treatments led to inhibition of Akt phosphorylation and its downstream proteins and rapamycin treatments similarly inhibited the phosphorylation of Tor‐linked downstream proteins. These findings support our hypothesis that TiO₂NPs influence Akt/Tor signaling in silk glands. The significance of this work is identification of specific sites of TiO₂NPs actions.