Reduction reactions and densification during in situ TEM heating of iron oxide nanochains.

The reduction reactions and densification of nanochains assembled from γ-Fe2O3 nanoparticles were investigated using in situ transmission electron microscopy (TEM). Morphological changes and reduction of the metal oxide nanochains were observed during in situ TEM annealing through simultaneous imaging and quantitative analysis of the near-edge fine structures of Fe L2,3 absorption edges acquired by spatially resolved electron energy loss spectroscopy. A change in the oxidation states during annealing of the iron oxide nanochains was observed with phase transformations due to continuous reduction from Fe2O3 over Fe3O4, FeO to metallic Fe. Phase transitions during the in situ heating experiments were accompanied with morphological changes in the nanochains, specifically rough-to-smooth surface transitions below 500 °C, neck formation between adjacent particles around 500 °C, and subsequent neck growth. At higher temperatures, coalescence of FeO particles was observed, representing densification.

Novel multi-functional europium-doped gadolinium oxide nanoparticle aerosols facilitate the study of deposition in the developing rat lung.

Ambient ultrafine particulate matter (UPM), less than 100 nm in size, has been linked to the development and exacerbation of pulmonary diseases. Age differences in susceptibility to UPM may be due to a difference in delivered dose as well as age-dependent differences in lung biology and clearance. In this study, we developed and characterized aerosol exposures to novel metal oxide nanoparticles containing lanthanides to study particle deposition in the developing postnatal rat lung. Neonatal, juvenile and adult rats (1, 3 and 12 weeks old) were nose only exposed to 380 µg m(-3) of ∼30 nm europium doped gadolinium oxide nanoparticles (Gd2O3:Eu(3+)) for 1 h. The deposited dose in the nose, extrapulmonary airways and lungs was determined using inductively-coupled plasma mass spectroscopy. The dose of deposited particles was significantly greater in the juvenile rats at 2.22 ng per g body weight compared to 1.47 ng per g and 0.097 ng per g for the adult and neonate rats, respectively. Toxicity was investigated in bronchoalveolar lavage fluid (BALF) by quantifying recovered cell types, and measuring lactate dehydrogenase activity and total protein. The toxicity data suggests that the lanthanide particles were not acutely toxic or inflammatory with no increase in neutrophils or lactate dehydrogenase activity at any age. Juvenile and adult rats had the same mass of deposited NPs per gram of lung tissue, while neonatal rats had significantly less NPs deposited per gram of lung tissue. The current study demonstrates the utility of novel lanthanide-based nanoparticles to study inhaled particle deposition in vivo and has important implications for nanoparticles delivery to the developing lung either as therapies or as a portion of particulate matter air pollution.

Influence of particle size on persistence and clearance of aerosolized silver nanoparticles in the rat lung.

The growing use of silver nanoparticles (AgNPs) in consumer products raises concerns about potential health effects. This study investigated the persistence and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m(3), respectively. Rat lung tissue was assessed for silver accumulations using inductively-coupled plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field microscopy. Involvement of tissue macrophages was assessed by scoring of silver staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the greatest number of silver positive BALF macrophages at 56 days post-exposure. While there was a significant decrease in the amount of silver in lung tissue at 56 days post-exposure compared with 1 day following exposure, at least 33% of the initial delivered dose was still present for both AgNPs. Regardless of particle size, silver was predominantly localized within the terminal bronchial/alveolar duct junction region of the lung associated with extracellular matrix and within epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a persistence of silver in the lung at 56 days post-exposure and local deposition as well as accumulation of silver at the terminal bronchiole alveolar duct junction. Further the smaller particles, 20 nm AgNP, produced a greater silver burden in BALF macrophages as well as greater persistence of silver positive macrophages at later timepoints (21 and 56 days).

Ultra-long Magnetic Nanochains for Highly Efficient Arsenic Removal from Water.

The contamination of drinking water with naturally occurring arsenic is a global health threat. Filters that are packed with adsorbent media with a high affinity for arsenic have been used to de-contaminate water - generally iron or aluminium oxides are favored materials. Recently, nanoparticles have been introduced as adsorbent media due to their superior efficiency compared to their bulk counter-parts. An efficient nanoadsorbent should ideally possess high surface area, be easy to synthesize, and most importantly offer a high arsenic removal capacity. Achieving all the key features in a single step synthesis is an engineering challenge. We have successfully engineered such a material in the form of nanochains synthesized via a one step flame synthesis. The ultra-long γ-Fe2O3 nanochains possess high surface area (151.12 m2 g-1), large saturation magnetization (77.1 emu g-1) that aids in their gas phase self-assembly into long chains in an external magnetic field, along with an extraordinary arsenic removal capacity (162 mg.g-1). A filter made with this material exhibited a relatively low-pressure drop and very little break-through of the iron oxide across the filter.

"Smart" theranostic lanthanide nanoprobes with simultaneous up-conversion fluorescence and tunable T1-T2 magnetic resonance imaging contrast and near-infrared activated photodynamic therapy.

The current work reports a type of "smart" lanthanide-based theranostic nanoprobe, NaDyF4:Yb(3+)/NaGdF4:Yb(3+),Er(3+), which is able to circumvent the up-converting poisoning effect of Dy(3+) ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent.

Potential toxicity of up-converting nanoparticles encapsulated with a bilayer formed by ligand attraction.

The cellular toxicity of nanoparticles that were capped with a bilayered ligand was studied using an up-converting (UC) phosphor material as a representative nanoparticle (NP). The results indicate that although UC NPs are known to be nontoxic, the toxicity of the NPs depends strongly on ligand coordination conditions, in addition to the other commonly known parameters such as size, structure, surface charge etc. Oleate-capped hydrophobic NaYF4:Yb,Er NPs were surface modified to yield three extreme conditions: bare particles that were stripped of the oleate ligands; particles with covalently bound poly(ethylene glycol) (PEG) ligands; and particles with an bilayer of PEG-oleate ligands using the oleate surface group that was remained after synthesis. It was found that the bare particles and the covalent PEG NPs induced little toxicity. However, particles that were rendered biocompatible by forming a bilayer with an amphiphilic ligand (i.e., PEG-oleate) resulted in significant cell toxicity. These findings strongly suggest that the PEG-oleate group dissociated from the bilayered oleate-capped NPs, resulting in significant toxicity by exposing the hydrophobic oleate-capped NPs to the cell. Based on results with bare particles, the NaLnF4:Yb,Er (Ln = Y, Gd) up-converting phosphors are essentially less-toxic. Capping and functionalizing these particles with ligand intercalation may, however, not be a suitable method for rendering the NPs suitable for bioapplication as the ligand can potentially dissociate upon cellular interaction, leading to significant toxicity.

NaGdF4:Eu3+ Nanoparticles for Enhanced X-ray Excited Optical Imaging.

X-ray luminescent nanoparticles (NPs), including lanthanide fluorides, have been evaluated for application to deep tissue in vivo molecular imaging using optical tomography. A combination of high material density, higher atomic number and efficient NIR luminescence from compatible lanthanide dopant ions indicates that particles that consist of ALnF4 (A = alkaline, Ln = lanthanide element) may offer a very attractive class of materials for high resolution, deep tissue imaging with X-ray excitation. NaGdF4:Eu3+ NPs produced an X-ray excited luminescence that was among the most efficient of nanomaterials that have been studied thus far. We have systematically studied factors such as (a) the crystal structure that changes the lattice environment of the doped Eu3+ ions within the unit cell; and extrinsic factors such as (b) a gold coating (with attendant biocompatibility) that couples to a plasmonic excitation, and (c) changes in the NPs surface properties via changes in the pH of the suspending medium-all with a significant impact on the X-ray excited luminescence of NaGdF4:Eu3+NPs. The luminescence from an optimally doped hexagonal phase NaGdF4:Eu3+ nanoparticle was 25% more intense compared to that of a cubic structure. We observed evidence of plasmonic reabsorption of midwavelength emission by a gold coating on hexagonal NaGdF4:Eu3+ NPs; fortunately, the NaGdF4:Eu3+ @Au core-shell NPs retained the efficient 5D0→7F4 NIR (692 nm) luminescence. The NaGdF4:Eu3+ NPs exhibited sensitivity to the ambient pH when excited by X-rays, an effect not seen with UV excitation. The sensitivity to the local environment can be understood in terms of the sensitivity of the excitons that are generated by the high energy X-rays (and not by UV photons) to crystal structure and to the surface state of the particles.

Sublethal effects of CuO nanoparticles on Mozambique tilapia (Oreochromis mossambicus) are modulated by environmental salinity.

The increasing use of manufactured nanoparticles (NP) in different applications has triggered the need to understand their putative ecotoxicological effects in the environment. Copper oxide nanoparticles (CuO NP) are toxic, and induce oxidative stress and other pathophysiological conditions. The unique properties of NP can change depending on the characteristics of the media they are suspended in, altering the impact on their toxicity to aquatic organisms in different environments. Here, Mozambique tilapia (O. mossambicus) were exposed to flame synthesized CuO NP (0.5 and 5 mg · L(-1)) in two environmental contexts: (a) constant freshwater (FW) and (b) stepwise increase in environmental salinity (SW). Sublethal effects of CuO NP were monitored and used to dermine exposure endpoints. Fish exposed to 5 mg · L(-1) CuO in SW showed an opercular ventilation rate increase, whereas fish exposed to 5 mg · L(-1) in FW showed a milder response. Different effects of CuO NP on antioxidant enzyme activities, accumulation of transcripts for metal-responsive genes, GSH ∶ GSSG ratio, and Cu content in fish gill and liver also demonstrate that additive osmotic stress modulates CuO NP toxicity. We conclude that the toxicity of CuO NP depends on the particular environmental context and that salinity is an important factor for modulating NP toxicity in fish.

Novel lanthanide-labeled metal oxide nanoparticles improve the measurement of in vivo clearance and translocation.

The deposition, clearance and translocation of europium-doped gadolinium oxide nanoparticles in a mouse lung were investigated experimentally. Nanoparticles were synthesized by spray flame pyrolysis. The particle size, crystallinity and surface properties were characterized. Following instillation, the concentrations of particles in organs were determined with inductively coupled plasma mass spectrometry. The protein corona coating the nanoparticles was found to be similar to the coating on more environmentally relevant nanoparticles such as iron oxide. Measurements of the solubility of the nanoparticles in surrogates of biological fluids indicated very little propensity for dissolution, and the elemental ratio of particle constituents did not change, adding further support to the contention that intact nanoparticles were measured. The particles were intratracheally instilled into the mouse lung. After 24 hours, the target organs were harvested, acid digested and the nanoparticle mass in each organ was measured by inductively coupled plasma mass spectrometry (ICP-MS). The nanoparticles were detected in all the studied organs at low ppb levels; 59% of the particles remained in the lung. A significant amount of particles was also detected in the feces, suggesting fast clearance mechanisms. The nanoparticle system used in this work is highly suitable for quantitatively determining deposition, transport and clearance of nanoparticles from the lung, providing a quantified measure of delivered dose.

Cytotoxic and genotoxic characterization of titanium dioxide, gadolinium oxide, and poly(lactic-co-glycolic acid) nanoparticles in human fibroblasts.

Engineered nanomaterials have become prevalent in our everyday life. While the popularity of using nanomaterials in consumer products continues to rise, increasing awareness of nanotoxicology has also fuelled efforts to accelerate our understanding of the ill effects that different nanomaterials can bring to biological systems. In this study, we investigated the potential cytotoxicity and genotoxicity of three nanoparticles: titanium dioxide (TiO(2)), terbium-doped gadolinium oxide (Tb-Gd(2)O(3)), and poly(lactic-co-glycolic acid) (PLGA). To evaluate nanoparticle-induced genotoxicity more realistically, a human skin fibroblast cell line (BJ) with less mutated genotype compared with cancer cell line was used. The nanoparticles were first characterized by size, morphology, and surface charge. Cytotoxicity effects of the nanoparticles were then evaluated by monitoring the proliferation of treated BJ cells. Genotoxic influence was ascertained by profiling DNA damage via detection of γH2AX expression. Our results suggested that both TiO(2) and Tb-Gd(2)O(3) nanoparticles induced cytotoxicity in a dose dependent way on BJ cells. These two nanomaterials also promoted genotoxicity via DNA damage. On the contrary, PLGA nanoparticles did not induce significant cytotoxic or genotoxic effects on BJ cells.

NaDyF4 Nanoparticles as T2 Contrast Agents for Ultrahigh Field Magnetic Resonance Imaging.

A major limitation of the commonly used clinical MRI contrast agents (CAs) suitable at lower magnetic field strengths (<3.0 T) is their inefficiency at higher fields (>7 T), where next-generation MRI scanners are going. We present dysprosium nanoparticles (ß-NaDyF4 NPs) as T2 CAs suitable at ultrahigh fields (9.4 T). These NPs effectively enhance T2 contrast at 9.4 T, which is 10-fold higher than the clinically used T2 CA (Resovist). Evaluation of the relaxivities at 3 and 9.4 T show that the T2 contrast enhances with an increase in NP size and field strength. Specifically, the transverse relaxivity (r2) values at 9.4 T were ∼64 times higher per NP (20.3 nm) and ∼6 times higher per Dy(3+) ion compared to that at 3 T, which is attributed to the Curie spin relaxation mechanism. These results and confirming phantom MR images demonstrate their effectiveness as T2 CAs in ultrahigh field MRIs.

Bimodal magnetic-fluorescent probes for bioimaging.

Fluorescent optical probes have been intensively used in the area of bio-imaging. In this review article, we describe the recent advancements in the synthesis and application of bimodal magnetic-fluorescent probes for bioimaging. The bimodal probes consist of fluorescent [semiconducting quantum dots (e.g., CdSe/ZnS) or rare-earth doped (e.g., NaYF(4) :Yb,Er)] nanoparticles (NPs) and magnetic (iron oxide or gadolinium based) NPs for optical and magnetic resonance (MR) imaging.

Comparative cytotoxicity evaluation of lanthanide nanomaterials on mouse and human cell lines with metabolic and DNA-quantification assays.

Lanthanide nanomaterials are considered a less toxic alternative to quantum dots for bioimaging applications. This study evaluated the cytotoxicity of terbium (Tb)-doped gadolinium oxide (Gd(2)O(3)) and dysprosium oxide (Dy(2)O(3)) nanoparticles exposed to human (BEAS-2B) and mouse (L929) cell lines at a concentration range of 200-2000 µg/ml for 48 h. Two assay methods were utilized-WST-8 assay (colorimetric) based on mitochondrial metabolic activity and Pico-Green assay (fluorescence), which measures total DNA content. The authors' data showed that Tb-doped Gd(2)O(3) nanoparticles were consistently more toxic than Tb-doped Dy(2)O(3) nanoparticles. However, exposure to these nanomaterials caused a decrease in proliferation rate for both cell lines rather than a net loss of viable cells after 48 h of exposure. Additionally, there was some degree of discrepancy observed with the two assay methods. For the mouse L929 cell line, the WST-8 assay yielded consistently lower proliferation rates compared to the Pico-Green assay, whereas the opposite trend was observed for the human BEAS-2B cell line. This could arise because of the differential effects of these nanoparticles on the metabolism of L929 and BEAS-2B cells, which in turn may translate to differences in their postexposure proliferation rates. Hence, the Pico-Green assay could have an advantage over the WST-8 assay because it is not skewed by the differential effects of nanomaterials on cellular metabolism.

Gadolinium oxide ultranarrow nanorods as multimodal contrast agents for optical and magnetic resonance imaging.

We demonstrate a simple synthetic strategy for the fabrication of single-phase rare earth (RE) doped gadolinium oxide (Gd(2)O(3):RE where RE = terbium (Tb), ytterbium (Yb), and erbium (Er)) nanorods (NRs) as multimodal imaging probes. The NRs are ultranarrow and exhibit both emission and magnetic characteristics. The Tb-doped and Yb/Er-codoped Gd(2)O(3) NRs exhibit down- and up-conversion fluorescence respectively, and also exhibit paramagnetism. Importantly, these codoped NRs possess excellent magnetic characteristics, as shown in their longitudinal relaxation time (T1) -weighted image contrast, which is closer to that of commercial Gadovist for magnetic resonance imaging (MRI) applications. This property opens up new avenues in the development of contrast agents.

In vitro cytotoxicity evaluation of biomedical nanoparticles and their extracts.

The present study presents a new approach for evaluating in vitro cytotoxicity of nanoparticles. The approach is based on American National Standard ISO 10993-5. Hepatoma HepG2 and fibroblast NIH3T3 cell lines were incubated with nanoparticles, and their associated extracts were derived at 70 and 121 degrees C. Nanoparticles proposed as potential biomedical imaging probes were evaluated on the basis of the detection of metabolic activities and cell-morphology changes. In general, nanoparticles incubated directly with cells showed higher cytotoxicity than their associated extracts. CdSe and core-shell CdSe@ZnS quantum dots resulted in low cell viability for both cell lines. The cytotoxicity of the quantum dots was attributed to the Cd ion and the presence of the nanoparticle itself. A statistically significant (p < 0.05) decrease in cell viability was found in higher dosage concentrations. Rare earth nanoparticles and their extracts appear to affect NIH3T3 cells only, with cell viability as low as 71.4% +/- 4.8%. Magnetic nanoparticles have no observable effects on the cell viabilities for both cell lines. In summary, we found the following: (1) both direct incubation and extracts of nanoparticles are required for complete assessment of nanoparticle cytotoxicity, (2) the rare earth oxide nanoparticles are less cytotoxic than the Cd-based quantum dots, and (3) the extent of cytotoxicity is dependent upon the cell line.