Aerosol exposure at air-liquid-interface (AE-ALI) in vitro toxicity system characterisation: Particle deposition and the importance of air control responses.

Experimental systems allowing aerosol exposure (AE) of cell cultures at the air-liquid-interface (ALI) are increasingly being used to assess the toxicity of inhaled contaminants as they are more biomimetic than standard methods using submerged cultures, however, they require detailed characterisation before use. An AE-ALI system combining aerosol generation with a CULTEX® exposure chamber was characterised with respect to particle deposition and the cellular effects of filtered air (typical control) exposures. The effect of system parameters (electrostatic precipitator voltage, air flowrate to cells and insert size) on deposition efficiency and spatial distribution were investigated using ICP-MS and laser ablation ICP-MS, for an aerosol of CeO2 nanoparticles. Deposition varied with conditions, but appropriate choice of operating parameters produced broadly uniform deposition at suitable levels. The impact of air exposure duration on alveolar cells (A549) and primary small airway epithelial cells (SAECs) was explored with respect to LDH release and expression of selected genes. Results indicated that air exposures could have a significant impact on cells (e.g., cytotoxicity and expression of genes, including CXCL1, HMOX1, and SPP1) at relatively short durations (from 10 mins) and that SAECs were more sensitive. These findings indicate that detailed system characterisation is essential to ensure meaningful results.

Dietary uptake and effects of copper in Sticklebacks at environmentally relevant exposures utilizing stable isotope-labeled 65CuCl2 and 65CuO NPs.

Copper oxide nanoparticles (CuO NPs) accumulating in sediment can be taken up by invertebrates that serve as prey for fish. Thus, it is likely that the latter are exposed to CuO NPs via the gut. However, to this day it is unknown if CuO NPs can be taken up via the gastrointestinal tract and if and in which tissues/organs they accumulate. To address this knowledge gap, we synthesized CuO NPs enriched in the stable isotope 65Cu and incorporated them at low concentration (5 µg 65Cu g-1 ww food) into a practical diet prepared from worm homogenate, which was then fed to Three-spined Stickleback (Gasterosteus aculeatus) for 16 days. For comparison, fish were exposed to a diet spiked with a 65CuCl2 solution. Background Cu and newly taken up 65Cu in fish tissues/organs including gill, stomach, intestine, liver, spleen, gonad and carcass and feces were quantified by ICP-MS. In addition, expression levels of genes encoding for proteins related to Cu uptake, detoxification and toxicity (ctr-1, gcl, gr, gpx, sod-1, cat, mta and zo-1) were measured in selected tissues using RT-qPCR. The obtained results showed that feces of fish fed 65CuO NP-spiked diet contained important amounts of 65Cu. Furthermore, there was no significant accumulation of 65Cu in any of the analyzed internal organs, though 65Cu levels were slightly elevated in liver. No significant modulation in gene expression was measured in fish exposed to 65CuO NP-spiked diet, except for metallothionein, which was significantly upregulated in intestinal tissue compared to control fish. Altogether, our results suggests that dietary absorption efficiency of CuO NPs, their uptake across the gastrointestinal barrier into the organism, and effects on Cu-related genes is limited at low, environmentally relevant exposure doses (0.2 µg 65Cu -1 fish ww day-1).

Synthesis and in vivo evaluation of PEG-BP-BaYbF5 nanoparticles for computed tomography imaging and their toxicity.

Computed tomography (CT) is one of the most widespread imaging techniques in clinical use worldwide. CT contrast agents are administered to improve soft tissue contrast and highlight blood vessels. However, the range of CT contrast agents available in the clinic is limited and they suffer from short-circulation times and low k-edge values that result in the need for high doses for in vivo applications. Nanomaterials containing a mixture of electron-dense elements, such as BaYbF5 nanoparticles, have shown promise as more efficient CT contrast agents, but they require biocompatible coatings for biomedical applications. Here, we explore the use of a bifunctional PEG polymer (5 kDa) containing a terminal bisphosphonate (BP) anchor for efficient binding to the surface of BaYbF5 nanomaterials. The resulting PEG(5)-BP-BaYbF5 nanoparticles were synthesized and characterized using TEM, DLS, TGA, XRD and Z-potential measurements. Their in vitro stability was verified and their ability to produce CT contrast in a wide range of X-ray energies, covering preclinical and clinical scanners, was demonstrated. In vitro toxicity studies with PEG(5)-BP-BaYbF5 in the phagocytic pro-monocytic human cell line U937 did not identify toxic effects, even at high concentrations (30 mM). In vivo, PEG(5)-BP-BaYbF5 exhibited efficient CT contrast for angiography imaging, highlighting blood vessels and vascular organs, and long circulation times as expected from the PEG coating. However, at late time points (48 h), in vivo toxicity was observed. While the causes could not be completely elucidated, in vitro studies suggest that decomposition and release of Yb3+ and/or Ba2+ metal ions after decomposition of PEG(5)-BP-BaYbF5 may play a role. Overall, despite the promising CT contrast properties, our results suggest that BaYbF5 nanomaterials may suffer from significant long-term toxicities.

Acute toxicity of Zinc Oxide nanoparticles to silkworm (Bombyx mori L.).

Zinc Oxide nanoparticles (ZnO NPs) has been heavily used in the industry, and increasing concerns on the ecotoxicity has arisen due to the risk of release into the environment. In this work, silkworm was used here as a model organism to study the toxicity of ZnO NPs, due to the presence of a conserved immune response as well as a pharmacokinetics similar to mammals. Zn accumulation, biodistribution and toxicity in silkworms were monitored at different time points after a subcutaneous injection. The highest cumulative content of ZnO NPs was detected in the midgut. The results of catalytic activity studies confirmed that the antioxidant enzymes (SOD, CAT, GSH-PX) in midgut cells were expressed in response to ZnO NPs. The expression of genes (Dronc and Caspase-1) related to apoptosis was increased, while the Trt gene was down-regulated. A possible mechanism was proposed for toxicity of ZnO NPs to silkworms.

Core-Shell NaHoF4@TiO2 NPs: A Labeling Method to Trace Engineered Nanomaterials of Ubiquitous Elements in the Environment.

Understanding the fate and behavior of nanoparticles (NPs) in the natural environment is important to assess their potential risk. Single particle inductively coupled plasma mass spectrometry (spICP-MS) allows for the detection of NPs at extremely low concentrations, but the high natural background of the constituents of many of the most widely utilized nanoscale materials makes accurate quantification of engineered particles challenging. Chemical doping, with a less naturally abundant element, is one approach to address this; however, certain materials with high natural abundance, such as TiO2 NPs, are notoriously difficult to label and differentiate from natural NPs. Using the low abundance rare earth element Ho as a marker, Ho-bearing core -TiO2 shell (NaHoF4@TiO2) NPs were designed to enable the quantification of engineered TiO2 NPs in real environmental samples. The NaHoF4@TiO2 NPs were synthesized on a large scale (gram), at relatively low temperatures, using a sacrificial Al(OH)3 template that confines the hydrolysis of TiF4 within the space surrounding the NaHoF4 NPs. The resulting NPs consist of a 60 nm NaHoF4 core and a 5 nm anatase TiO2 shell, as determined by TEM, STEM-EDX mapping, and spICP-MS. The NPs exhibit excellent detectability by spICP-MS at extremely low concentrations (down to 1 × 10-3 ng/L) even in complex natural environments with high Ti background.

Sensitization, energy transfer and infra-red emission decay modulation in Yb3+-doped NaYF4 nanoparticles with visible light through a perfluoroanthraquinone chromophore.

Infra-red emission (980 nm) of sub 10 nm Yb3+-doped NaYF4 nanoparticles has been sensitized through the excitation of 2-hydroxyperfluoroanthraquinone chromophore (1,2,3,4,5,6,7-heptafluro-8-hydroxyanthracene-9,10-dione) functionalizing the nanoparticle surface. The sensitization is achieved with a broad range of visible light excitation (400-600 nm). The overall near infra-red (NIR) emission intensity of Yb3+ ions is increased by a factor 300 as a result of the broad and strong absorption of the chromophore compared with ytterbium's intrinsic absorption. Besides the Yb3+ NIR emission, the hybrid composite shows organic chromophore-based visible emission in the orange-red region of the spectrum. We observe the energy migration process from the sensitized Yb3+ ions at the surface to those in the core of the particle using time-resolved optical spectroscopy. This highlights that the local environments for emitting Yb3+ ions at the surface and center of the nanoparticle are not identical, which causes important differences in the NIR emission dynamics. Based on the understanding of these processes, we suggest a simple strategy to control and modulate the decay time of the functionalized Yb3+-doped nanoparticles over a relatively large range by changing physical or chemical parameters in this model system.

Correlations of single nucleotide polymorphisms of CRYAA and CRYAB genes with the risk and clinicopathological features of children suffering from congenital cataract.

BACKGROUND: The study aims to explore the correlations of the single nucleotide polymorphisms (SNPs) of CRYAA and CRYAB with the risk and clinicopathological features of children with congenital cataract. METHODS: The study enrolled 168 children diagnosed as congenital cataract (case group) and 172 normal children (control group) from May 2015 to May 2016. Genomic DNA extraction was performed using a QIAamp DNA blood mini kit. Polymerase chain reaction (PCR) products were genotyped using an ABI direct sequencer. Haplotype, allele, and genotype frequencies of CRYAA and CRYAB gene polymorphisms analyses were carried out using the SHEsis software. Logistic regression analysis was performed in order to analyze the risk factors for children suffering from congenital cataract. RESULTS: Presence of significant differences between the case and control groups' genotype and allele frequencies of CRYAA rs7278468 and CRYAB rs370803064/rs387907338. TA of CRYAB gene might increase congenital cataract risk in children, while GCG of CRYAA gene and GC of CRYAB gene might decrease congenital cataract risk in children. CRYAA rs7278468, CRYAB rs370803064/rs387907338 polymorphisms were significantly correlated to uncorrected visual acuity, best-corrected visual acuity, nystagmus, visual axis opacification, microcornea, lens opacity, posterior capsular thickening, and degrees of posterior capsule opacification after operation in children with congenital cataract. Logistic regression analysis revealed that the T allele of CRYAA rs7278468, A allele of CRYAB rs370803064, T allele of CRYAB rs387907338, family history, and TA haplotype of CRYAB gene were risk factors for children with congenital cataract. CONCLUSION: Our findings demonstrated that CRYAA rs7278468 and CRYAB rs370803064/rs387907338 are correlated with the risk and clinicopathological features of children suffering from congenital cataract.

Synthesis, Characterization, and Application of Core-Shell Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm) Nanoparticle as Trimodal (MRI, PET/SPECT, and Optical) Imaging Agents.

Multimodal nanoparticulate materials are described, offering magnetic, radionuclide, and fluorescent imaging capabilities to exploit the complementary advantages of magnetic resonance imaging (MRI), positron emission tomography/single-photon emission commuted tomography (PET/SPECT), and optical imaging. They comprise Fe3O4@NaYF4 core/shell nanoparticles (NPs) with different cation dopants in the shell or core, including Co0.16Fe2.84O4@NaYF4(Yb, Er) and Fe3O4@NaYF4(Yb, Tm). These NPs are stabilized by bisphosphonate polyethylene glycol conjugates (BP-PEG), and then show a high transverse relaxivity (r2) up to 326 mM(-1) s(-1) at 3T, a high affinity to [(18)F]-fluoride or radiometal-bisphosphonate conjugates (e.g., (64)Cu and (99m)Tc), and fluorescent emissions from 500 to 800 nm under excitation at 980 nm. The biodistribution of intravenously administered particles determined by PET/MR imaging suggests that negatively charged Co0.16Fe2.84O4@NaYF4(Yb, Er)-BP-PEG (10K) NPs cleared from the blood pool more slowly than positively charged NPs Fe3O4@NaYF4(Yb, Tm)-BP-PEG (2K). Preliminary results in sentinel lymph node imaging in mice indicate the advantages of multimodal imaging.

Aluminium hydroxide stabilised MnFe2O4 and Fe3O4 nanoparticles as dual-modality contrasts agent for MRI and PET imaging.

Magnetic nanoparticles (NPs) MnFe2O4 and Fe3O4 were stabilised by depositing an Al(OH)3 layer via a hydrolysis process. The particles displayed excellent colloidal stability in water and a high affinity to [(18)F]-fluoride and bisphosphonate groups. A high radiolabeling efficiency, 97% for (18)F-fluoride and 100% for (64)Cu-bisphosphonate conjugate, was achieved by simply incubating NPs with radioactivity solution at room temperature for 5 min. The properties of particles were strongly dependant on the thickness and hardness of the Al(OH)3 layer which could in turn be controlled by the hydrolysis method. The application of these Al(OH)3 coated magnetic NPs in molecular imaging has been further explored. The results demonstrated that these NPs are potential candidates as dual modal probes for MR and PET. In vivo PET imaging showed a slow release of (18)F from NPs, but no sign of efflux of (64)Cu.

Bisphosphonate-anchored PEGylation and radiolabeling of superparamagnetic iron oxide: long-circulating nanoparticles for in vivo multimodal (T1 MRI-SPECT) imaging.

The efficient delivery of nanomaterials to specific targets for in vivo biomedical imaging is hindered by rapid sequestration by the reticuloendothelial system (RES) and consequent short circulation times. To overcome these two problems, we have prepared a new stealth PEG polymer conjugate containing a terminal 1,1-bisphosphonate (BP) group for strong and stable binding to the surface of ultrasmall-superparamagnetic oxide nanomaterials (USPIOs). This polymer, PEG(5)-BP, can be used to exchange the hydrophobic surfactants commonly used in the synthesis of USPIOs very efficiently and at room temperature using a simple method in 1 h. The resulting nanoparticles, PEG(5)-BP-USPIOs are stable in water or saline for at least 7 months and display a near-zero ζ-potential at neutral pH. The longitudinal (r(1)) and transverse (r(2)) relaxivities were measured at a clinically relevant magnetic field (3 T), revealing a high r(1) of 9.5 mM(-1) s(-1) and low r(2)/r(1) ratio of 2.97, making these USPIOs attractive as T1-weighted MRI contrast agents at high magnetic fields. The strong T1-effect was demonstrated in vivo, revealing that PEG(5)-BP-USPIOs remain in the bloodstream and enhance its signal 6-fold, allowing the visualization of blood vessels and vascular organs with high spatial definition. Furthermore, the optimal relaxivity properties allow us to inject a dose 4 times lower than with other USPIOs. PEG(5)-BP-USPIOs can also be labeled using a radiolabeled-BP for visualization with single photon emission computed tomography (SPECT), and thus affording dual-modality contrast. The SPECT studies confirmed low RES uptake and long blood circulation times (t(1/2) = 2.97 h). These results demonstrate the potential of PEG(5)-BP-USPIOs for the development of targeted multimodal imaging agents for molecular imaging.

Surfactant-free scalable synthesis of hierarchically spherical Co3O4 superstructures and their enhanced lithium-ion storage performances.

Unique hierarchically porous spherical Co(3)O(4) superstructures were synthesized via a surfactant-free hydrothermal process followed by a calcination treatment, in which the concentration of reactant cobalt (II) nitrate hexahydrate is a key factor affecting the morphology of products. X-ray powder diffraction, electron microscopies (TEM and SEM), and thermogravimetric analysis were employed to investigate the formation of Co(3)O(4) spherical superstructures. Our results suggest that they formed from numerous cubic Co(3)O(4) nanocrystals via an oriented attachment mechanism. These superstructures exhibit a high specific capacity of 1750 mA h g(-1) after the first charge-discharge cycle, and the capacity retention remains at a constant of 1600 mA h g(-1) at 0.2 C after 50 cycles. The facile, scalable, energy-efficient and environmentally friendly nature of the presented approach renders it particularly attractive from a technological standpoint. In addition, this scalable and facile synthesis method could be extended to the preparation of other transition metal oxides with specific morphologies and surface textures.

Nanodiamond promotes surfactant-mediated triglyceride removal from a hydrophobic surface at or below room temperature.

We demonstrate that ca. 5 nm nanodiamond particles dramatically improve triglyceride lipid removal from a hydrophobic surface at room temperature using either anionic or nonionic surfactants. We prepare nanodiamond-surfactant colloids, measure their stability by dynamic light scattering and use quartz crystal microbalance-dissipation, a technique sensitive to surface mass, in order to compare their ability to remove surface-bound model triglyceride lipid with ionic and nonionic aqueous surfactants at 15-25 °C. Oxidized, reduced, ω-alkylcarboxylic acid, and ω-alkylamidoamine surface-modified adducts are prepared, and then characterized by techniques including (13)C cross-polarization (CP) magic-angle spinning (MAS) NMR. Clear improvement in removal of triglyceride was observed in the presence of nanodiamond, even at 15 °C, both with nanodiamond-surfactant colloids, and by prior nanoparticle deposition on interfacial lipid, showing that nanodiamonds are playing a crucial role in the enhancement of the detergency process, providing unique leads in the development of new approaches to low-temperature cleaning.

Dynamic equilibria in solvent-mediated anion, cation and ligand exchange in transition-metal coordination polymers: solid-state transfer or recrystallisation?

The solution properties of a series of transition-metal-ligand coordination polymers [ML(X)(n)](infinity) [M=Ag(I), Zn(II), Hg(II) and Cd(II); L=4,4'-bipyridine (4,4'-bipy), pyrazine (pyz), 3,4'-bipyridine (3,4'-bipy), 4-(10-(pyridin-4-yl)anthracen-9-yl)pyridine (anbp); X=NO(3) (-), CH(3)COO(-), CF(3)SO(3) (-), Cl(-), BF(4) (-); n=1 or 2] in the presence of competing anions, metal cations and ligands have been investigated systematically. Providing that the solubility of the starting complex is sufficiently high, all the components of the coordination polymer, namely the anion, the cation and the ligand, can be exchanged on contact with a solution phase of a competing component. The solubility of coordination polymers is a key factor in the analysis of their reactivity and this solubility depends strongly on the physical properties of the solvent and on its ability to bind metal cations constituting the backbone of the coordination polymer. The degree of reversibility of these solvent-induced anion-exchange transformations is determined by the ratio of the solubility product constants for the starting and resultant complexes, which in turn depend upon the choice of solvent and the temperature. The extent of anion exchange is controlled effectively by the ratio of the concentrations of incoming ions to outgoing ions in the liquid phase and the solvation of various constituent components comprising the coordination polymer. These observations can be rationalised in terms of a dynamic equilibrium of ion exchange reactions coupled with Ostwald ripening of crystalline products. The single-crystal X-ray structures of [Ag(pyz)ClO(4)](infinity) (1), {[Ag(4,4'-bipy)(CF(3)SO(3))]CH(3)CN}(infinity) (2), {[Ag(4,4'-bipy)(CH(3)CN)]ClO(4) 0.5 CH(3)CN}(infinity) (3), metal-free anbp (4), [Ag(anbp)NO(3)(H(2)O)](infinity) (5), {[Cd(4,4'-bipy)(2)(H(2)O)(2)](NO(3))(2)4 H(2)O}(infinity) (6) and {[Zn(4,4'-bipy)SO(4)(H(2)O)(3)] 2 H(2)O}(infinity) (7) are reported.

Selective synthesis and characterization of single-crystal silver molybdate/tungstate nanowires by a hydrothermal process.

Selective synthesis of uniform single crystalline silver molybdate/tungstate nanorods/nanowires in large scale can be easily realized by a facile hydrothermal recrystallization technique. The synthesis is strongly dependent on the pH conditions, temperature, and reaction time. The phase transformation was examined in details. Pure Ag(2)MoO(4) and Ag(6)Mo(10)O(33) can be easily obtained under neutral condition and pH 2, respectively, whereas other mixed phases of Mo(17)O(47), Ag(2)Mo(2)O(7,) Ag(6)Mo(10)O(33) were observed under different pH conditions. Ag(6)Mo(10)O(33) nanowires with uniform diameter 50-60 nm and length up to several hundred micrometers were synthesized in large scale for the first time at 140 degrees C. The melting point of Ag(6)Mo(10)O(33) nanowires were found to be about 238 degrees C. Similarly, Ag(2)WO(4), and Ag(2)W(2)O(7) nanorods/nanowires can be selectively synthesized by controlling pH value. The results demonstrated that this route could be a potential mild way to selectively synthesize various molybdate nanowires with various phases in large scale.