Gadolinium Oxide Nanoparticles Research Articles

Functional Nanoparticles Translocation Into Cell and Adhesion Force Curve Analysis

The aim of this research is to investigate the cell translocation of two functional nanoparticles (barium sulfate (BaSO4NPs), europium (III) doped gadolinium oxide nanoparticles (Gd2O3@EuNPs)) into A549 cells by Bio-Atomic Force Microscopy (Bio-AFM). Successful cell translocation of these two nanoparticles are ensured from the measurement of changes in the cell surface roughness and interaction (extension), retraction forces from the vertical deflection of tip towards substrate surfaces through force-distance curve slope analysis. Measurement of typical adhesion forces (i.e., extension and retraction) between the tip-substrate (0.0963 and 1.155 nN), tip-A549 cell substrate (0.1177 and 2.468 nN), tip-Gd2O3@EuNPs/A549 substrate (0.0785 and 0.4276 nN) and tip-BaSO4NPs/A549 substrate (0.518 and 6.838 nN) confirms the successful cell translocation of functional nanoparticles into A549 cells. Further the nanoscale resolution of topographical height and 3D images evinces the surface characteristics of normal A549 cells and nanoparticles translocated A549 cells.

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.

Rapid Synthesis of PEGylated Ultrasmall Gadolinium Oxide Nanoparticles for Cell Labeling and Tracking with MRI

Ultrasmall paramagnetic Gd(2)O(3) nanoparticles have been developed as contrast agents for molecular and cellular preclinical MRI procedures. These small particles (mean diameter <5 nm) have the highest Gd density of all paramagnetic contrast agents. They generate strong positive contrast enhancement in T(1)-weighted MRI. Signal enhancement is modulated by the interactions of water molecules with Gd, and very small particles provide the optimal surface-to-volume ratios necessary to reach high relaxivities. Conventional Gd(2)O(3) nanocrystal synthesis techniques, and subsequent polyethylene glycol (PEG) grafting procedures are usually time-consuming and recovery losses are also limitative. The present study reports on a new, fast, and efficient one-pot Gd(2)O(3) synthesis technique that provides PEGylated nanoparticles of very small size (mean diameter = 1.3 nm). Readily coated with PEG, the particles are colloidally stable in aqueous media and provide high longitudial relaxivities and small r(2)/r(1) ratios (r(1) = 14.2 mM(-1) s(-1) at 60 MHz; r(2)/r(1) = 1.20), ideal for T(1)-weighted MRI. In this study, F98 brain cancer cells (glioblastoma multiforme) were labeled with the contrast agent and implanted in vivo (mice brains). The labeled cells appeared positively contrasted at least 48 h after implantation. Each one of the implanted animals developed a brain tumor. The performance of PEG-Gd(2)O(3) was also compared with that of commercially available iron oxide nanoparticles. This study demonstrated that ultrasmall PEG-Gd(2)O(3) nanoparticles provide strong positive contrast enhancement in T(1)-weighted imaging, and allow the visualization of labeled cells implanted in vivo.

Concurrent Dual Contrast for Cellular Magnetic Resonance Imaging Using Gadolinium Oxide and Iron Oxide Nanoparticles

Rationale and Objectives. Concurrent visualization of differential targets in cellular and molecular imaging is valuable for resolving processes spatially and temporally, as in monitoring different cell subtypes. The purpose of this study was to demonstrate concurrent, dual (positive and negative) contrast visualization on magnetic resonance imaging (MRI) of two colocalized cell populations labeled with Gadolinium “Gd” oxide and iron “Fe” oxide nanoparticles. Materials and Methods. Human aortic endothelial cells (EC) and smooth muscle cells (SMC) were labeled with various concentrations of Gd oxide and Fe oxide, respectively. MRI on single- or mixed-cell samples was performed at 7 tesla. Proper cell phenotype expressions, cell uptake of contrast agents, and the effect of labeling on cell viability and proliferation were also determined. Results. Both contrast agents were efficiently taken up by cells, with viability and proliferation largely unaffected. On MRI, the positive contrast associated with Gd oxide-labeled EC and negative contrast associated with Fe oxide-labeled SMC discriminated the presence of each cell type, whether it existed alone or colocalized in a mixed-cell sample. Conclusion. It is feasible to use Gd oxide and Fe oxide for dual contrast and concurrent discrimination of two colocalized cell populations on MRI at 7 tesla.

Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes

We have previously shown that gadolinium oxide (Gd2O3) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd2O3 nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd2O3 nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd2O3 nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd2O3 nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.

Human Aortic Endothelial Cell Labeling with Positive Contrast Gadolinium Oxide Nanoparticles for Cellular Magnetic Resonance Imaging at 7 Tesla

Positive T₁ contrast using gadolinium (Gd) contrast agents can potentially improve detection of labeled cells on magnetic resonance imaging (MRI). Recently, gadolinium oxide (Gd₂O₃) nanoparticles have shown promise as a sensitive T₁ agent for cell labeling at clinical field strengths compared to conventional Gd chelates. The objective of this study was to investigate Gado CELLTrack, a commercially available Gd₂O₃ nanoparticle, for cell labeling and MRI at 7 T. Relaxivity measurements yielded r1 = 4.7 s⁻¹ mM⁻¹ and r₂/r₁ = 6.2. Human aortic endothelial cells were labeled with Gd₂O₃ at various concentrations and underwent MRI from 1 to 7 days postlabeling. The magnetic resonance relaxation times T₁ and T₂ of labeled cell pellets were measured. Cellular contrast agent uptake was quantified by inductively coupled plasma-atomic emission spectroscopy, which showed very high uptake compared to conventional Gd compounds. MRI demonstrated significant positive T₁ contrast and stable labeling on cells. Enhancement was optimal at low Gd concentrations, attained in the 0.02 to 0.1 mM incubation concentration range (corresponding cell uptake was 7.26 to 34.1 pg Gd/cell). Cell viability and proliferation were unaffected at the concentrations tested and up to at least 3 days postlabeling. Gd₂O₃ is a promising sensitive and stable positive contrast agent for cellular MRI at 7 T.

Magnetically induced optical activity and dichroism of gadolinium oxide nanoparticle–based ferrofluids

The present work reports on magnetically induced optical activity (such as Faraday rotation and linear dichroism) of pristine and gamma-irradiated gadolinium oxide (Gd2O3) nanoparticle–based ferrofluids. The ferrofluids were produced by dispersing N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB)-coated ∼9-nm-sized Gd2O3 particles in a carrier fluid of ethanol. The ferrofluids were then irradiated with 1.25 MeV energetic gamma rays (dose: 868 Gy and 2.635 kGy). Irradiation-led formation of a number of point defects was revealed through high resolution electron microscopy. The interaction of light with the ionized point defects is believed to have caused substantial improvement in the magneto-optic response of irradiated magnetic fluids.

Fluorescein-polyethyleneimine coated gadolinium oxide nanoparticles as T1 magnetic resonance imaging (MRI)–cell labeling (CL) dual agents

We report the synthesis, characterization and application of highly water-soluble fluorescein-polyethyleneimine (PEI) coated gadolinium oxide (Gd2O3) nanoparticles to magnetic resonance imaging (MRI) and cell labeling (CL). The average particle diameter and average hydrodynamic diameter were estimated to be 3.92 and 7.5 nm, respectively. Fluorescein-PEI was prepared from EDC/NHS coupling method. The surface coating was characterized by the FT-IR absorption spectrum and the surface coating amount was estimated to be 22.42 wt% from a TGA analysis, corresponding to 0.65 nm−2 grafting density. The fluorescein-PEI coated gadolinium oxide nanoparticles showed r1 and r2 of 6.76 and 20.27 s−1mM−1, respectively, and a strong fluorescence at ∼527 nm. A pronounced positive contrast enhancement was clearly observed in 3 tesla T1 MR images of a rat with a liver tumor after injection of an aqueous sample solution into a rat tail vein. After treatment of DU145 cells with a sample solution, a strong fluorescence in confocal images was also observed. These two results together confirm the excellent MRI-CL dual functionality of fluorescein-PEI coated gadolinium oxide nanoparticles.

Surface Modification of Gadolinium Oxide Thin Films and Nanoparticles using Poly(ethylene glycol)-Phosphate

The performance of nanomaterials for biomedical applications is highly dependent on the nature and the quality of surface coatings. In particular, the development of functionalized nanoparticles for magnetic resonance imaging (MRI) requires the grafting of hydrophilic, nonimmunogenic, and biocompatible polymers such as poly(ethylene glycol) (PEG). Attached at the surface of nanoparticles, this polymer enhances the steric repulsion and therefore the stability of the colloids. In this study, phosphate molecules were used as an alternative to silanes or carboxylic acids, to graft PEG at the surface of ultrasmall gadolinium oxide nanoparticles (US-Gd(2)O(3), 2-3 nm diameter). This emerging, high-sensitivity "positive" contrast agent is used for signal enhancement in T(1)-weighted molecular and cellular MRI. Comparative grafting assays were performed on Gd(2)O(3) thin films, which demonstrated the strong reaction of phosphate with Gd(2)O(3) compared to silane and carboxyl groups. Therefore, PEG-phosphate was preferentially used to coat US-Gd(2)O(3) nanoparticles. The grafting of this polymer on the particles was confirmed by XPS and FTIR. These analyses also demonstrated the strong attachment of PEG-phosphate at the surface of Gd(2)O(3), forming a protective layer on the nanoparticles. The stability in aqueous solution, the relaxometric properties, and the MRI signal of PEG-phosphate-covered Gd(2)O(3) particles were also better than those from non-PEGylated nanoparticles. As a result, reacting PEG-phosphate with Gd(2)O(3) particles is a promising, rapid, one-step procedure to PEGylate US-Gd(2)O(3) nanoparticles, an emerging "positive" contrast agent for preclinical molecular and cellular applications.

Impact of agglomeration on the relaxometric properties of paramagnetic ultra-smallgadolinium oxide nanoparticles

Ultra-small gadolinium oxide nanoparticles (US-Gd2O3) are used to provide ‘positive’ contrast effects in magnetic resonance imaging (MRI), andare being considered for molecular and cellular imaging applications. However,these nanoparticles can aggregate over time in aqueous medium, as well as wheninternalized into cells. This study is aimed at measuring in vitro, in aqueous medium,the impact of aggregation on the relaxometric properties of paramagnetic US-Gd2O3 particles. First, the nanoparticle core size as well as aggregation behaviour wasassessed by HRTEM. DLS (hydrodynamic diameter) was used to measurethe hydrodynamic diameter of nanoparticles and nanoaggregates. Therelaxometric properties were measured by NMRD profiling, as well as with 1H NMR relaxometers. Then, the positive contrast enhancement effect was assessed by usingmagnetic resonance scanners (at 1.5 and 7 T). At every magnetic field, the longitudinal relaxivity(r1) decreased upon agglomeration, while remaining high enough toprovide positive contrast. On the other hand, the transverse relaxivity(r2) slightly decreased at 0.47 and 1.41 T, but it was enhanced at higher fields (7and 11.7 T) upon agglomeration. All NMRD profiles revealed a characteristicrelaxivity peak in the range 60–100 MHz, suggesting the possibility to use US-Gd2O3 as an efficient‘positive-T1’ contrast agent at clinical magnetic fields (1–3 T), in spite of aggregation.

Size-induced effect upon the Néel temperature of the antiferro/paramagnetic transition in gadolinium oxide nanoparticles

In this paper, we demonstrate that cubic gadolinium oxide is paramagnetic and follows the Curie–Weiss law from 20 K to room temperature for particles size comprised between 3.5 and 60 nm. The largest particles (60 nm) possess the macroscopic behaviour of Gd oxide with a Neel temperature, TN, close to 18 K (Gd oxide is antiferromagnetic below TN, paramagnetic above). Then size-induced effects can be encountered only for particles smaller than 60 nm. We find that the finite-size scaling model used for describing the size evolution of the antiferro/paramagnetic transition is valid for sizes comprised between 3.5 and 35 nm with parameters in excellent agreement with those usually found for antiferromagnetic materials. The correlation length (3.6 nm) is of the order of magnitude of a few lattice parameters and the critical exponent λ is found equal to 1.3, a value very close to that predicted by the three dimensional Heisenberg model (λ=1.4).

Synthesis, characterization and effect of low energy Ar ion irradiation on gadolinium oxide nanoparticles

In this work, we report on the surfactant assisted synthesis of gadolinium oxide (Gd 2O 3) nanoparticles and their characterization through various microscopic and spectroscopic tools. Exhibiting a monoclinic phase, the nanoscale Gd 2O 3 particles are believed to be comprising of crystallites with an average size of ∼3.2 nm, as revealed from the X-ray diffraction analysis. The transmission electron microscopy has predicted a particle size of ∼9 nm and an interplanar spacing of ∼0.28 nm. Fourier transform infrared spectroscopy studies show that Gd–O inplane vibrations at 536.8 and 413.3 cm −1 were more prominent for 80-keV Ar-ion irradiated Gd 2O 3 nanosystem than unirradiated system. The photoluminescence (PL) spectra of irradiated specimen have revealed an improvement in the symmetry factor owing to significant enhancement of surface-trap emission, compared to the band-edge counterpart. Irradiation induced creation of point defects (oxygen vacancies) were predicted both from PL and electron paramagnetic resonance (EPR) studies. Further, the Raman spectra of the irradiated sample have exhibited notable vibrational features along with the evolution of a new peak at ∼202 cm −1. This can be ascribed to an additional Raman active vibrational response owing to considerable modification of the nanostructure surface as a result of ion bombardment. Probing nanoscale defects through prime spectroscopy tools would find a new avenue for precise tuning of physical properties with generation and annihilation of defects.

Characteristics of Gadolinium Oxide Nanoparticles as Contrast Agents for Terahertz Imaging

For the application of gadolinium oxide (Gd2O3) nanoparticles as terahertz contrast agents, their optical properties in a solvent were studied using terahertz time-domain spectroscopy. The power absorption and refractive index of the samples were measured with various concentrations of nanoparticles. The power absorption was extremely large, as much as three orders of magnitude higher than that of water, so that a few ppms of Gd2O3 nanoparticles were distinguished in terms of their power absorption capacity. The results show that the interaction between the terahertz electromagnetic waves and the Gd2O3 nanoparticles is strong enough to allow their exploitation as contrast agents for terahertz medical imaging.

Ultra‐small gadolinium oxide nanoparticles to image brain cancer cells in vivo with MRI

The majority of contrast agents used in magnetic resonance imaging (MRI) is based on the rare-earth element gadolinium. Gadolinium-based nanoparticles could find promising applications in pre-clinical diagnostic procedures of certain types of cancer, such as glioblastoma multiforme. This is one of the most malignant, lethal and poorly accessible forms of cancer. Recent advances in colloidal nanocrystal synthesis have led to the development of ultra-small crystals of gadolinium oxide (US-Gd(2)O(3), 2-3 nm diameter). As of today, this is the smallest and the densest of all Gd-containing nanoparticles. Cancer cells labeled with a sufficient quantity of this compound appear bright in T(1)-weighted MRI images. Here we demonstrate that US-Gd(2)O(3) can be used to label GL-261 glioblastoma multiforme cells, followed by localization and visualization in vivo using MRI. Very high amounts of Gd are efficiently internalized and retained in cells, as confirmed with TEM and ICP-MS. Labeled cells were visualized in vivo at 1.5 T using the chicken embryo model. This is one more step toward the development of "positively contrasted" cell tracking procedures with MRI.

Homogeneous dispersion of gadolinium oxide nanoparticles into a non-aqueous-based polymer by two surface treatments

Gadolinium oxide nanoparticles are more and more used. They can notably provide interesting fluorescence properties. Herein they are incorporated into a non-aqueous-based polymer, the poly(methyl methacrylate). Their dispersion within the polymer matrix is the key to improve the composite properties. As-received gadolinium oxide nanopowders cannot be homogeneously dispersed in such a polymer matrix. Two surface treatments are, therefore, detailed and compared to achieve a good stability of the nanoparticles in a non-aqueous solvent such as the 2-butanone. Then, once the liquid suspensions have been stabilized, they are used to prepare nanocomposites with homogeneous particles dispersion. The two approaches proposed are an hybrid approach based on the growth of a silica shell around the gadolinium oxide nanoparticles, and followed by a suitable silane functionalization; and a non-hybrid approach based on the use of surfactants. The surface treatments and formulations involved in both methods are detailed, adjusted and compared. Thanks to optical methods and in particular to the use of a ‘home made’ confocal microscope, the dispersion homogeneity within the polymer can be assessed. Both methods provide promising and conclusive results.

Ultra small Gd 2O 3 nanoparticles: Absorption and emission properties

In this paper, we report a facile method for synthesis of ultra small (1–3 nm) gadolinium oxide (Gd 2O 3) nanoparticles using citric acid (CA) as a capping agent. The dependence of nanoparticle (NP) size on the ratio between CA and gadolinium (Gd) is investigated. Absorption properties of the ultra small Gd 2O 3 NPs in UV region have four characteristic peaks at 312 nm, 274 nm, 253 nm and 228 nm. Finally, we show that the Gd 2O 3 nanoparticles synthesized by this method induce triplet emission (phosphorescence) from CA and EG in the NIR region.

Observation of green emission from Ce3+-doped gadolinium oxide nanoparticles

Green emission at around 500 nm is observed in Gd2O3:Ce3+ nanoparticles and the intensity is highly dependent on the concentration of Ce3+ in the nanoparticles. The luminescence of this emission displays both picosecond and millisecond lifetimes. The msec lifetime is over four orders of magnitude longer than typical luminescence lifetimes (10-40 ns) of Ce3+ in traditional Ce3+ doped phosphors and therefore likely originates from defect states. The picosecond lifetime is shorter than the typical Ce3+ value and is also likely due to defect or surface states. When the samples are annealed at 700 oC, this emission disappears possibly due to changes in the defect moieties or concentration. In addition, a blue emission at around 430 nm is observed in freshly-prepared Gd2O3 undoped nanoparticles which is attributed to the stabilizer, polyethylene glycol biscarboxymethyl ether. Upon aging, the undoped particles show similar emission to the doped particles with similar luminescence lifetimes. When Eu3+ ions are co-doped in Gd2O3:Ce nanoparticles, both the green emission and the emission at 612 nm from Eu3+ are observed.

Water‐Soluble Ultra‐Small Manganese Oxide Surface Doped Gadolinium Oxide (Gd2O3@MnO) Nanoparticles for MRI Contrast Agent

AbstractWe have developed ultra‐small gadolinium oxide (Gd2O3) nanoparticles, which are surface‐doped with manganese oxide (MnO) (abbreviated as Gd2O3@MnO). The surface‐doped nanoparticles ranged from 1 to 2 nm in diameter. They were further coated with hydrophilic biocompatible lactobionic acid. In‐vitro tests of the sample solution indicated clear dose‐dependent contrast enhancements in both T1 and T2 map images, showing that the nanoparticles may be used as both T1 and T2 MRI contrast agents. Their performance as a T1 MRI contrast agent was proved in vivo through T1 MR images of a mouse.

SU‐GG‐I‐149: Positive MRI Contrast Agent Based on Gd2O3 Nanoparticles for Cell Tracking

Purpose: In this study nanoparticles of gadolinium oxide have been investigated for intracellular uptake and capacity to generate a positive contrast. For this purpose two novel composed of a) silicon‐based nanocomposite polymer(NCP), b) Diethylene glycol (DEG) based coating material, both loaded with gadolinium(III) oxide (Gd2O3) nanoparticles were used. Method and Materials: This study would be involved with nanoparticles composed gadolinium (III) oxide, a) emulsified with a silicon‐based nanocomposite polymer and b) capped with Diethylene glycol (DEG) by polyol method starting from of Gd2O3 large particles, leading to Gd2O3 nano size capping with polymers. Prpoerties evaluation of nanoparticles were assessed previously by this group. Presently, cytotoxicity of gadolinium oxide nanoparticles in U‐87 MG cancer cells was evaluated. Furthermore relaxivity of particles in U‐87 cells were compared to particles in cell culture medium. Results: The results showed that Gd2O3‐labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. The slope of r1 relaxivity (1/T1) vs. concentration curve in cell samples and ccm of Gd2O3 (NCP)were 10.87 and 10.60 s−1mM−1 and for Gd2O3 (deg) were 13.99, 13.66 s−1mM−1 respectively. The slope of r2 relaxivity (1/T2) vs. concentration curve in cell samples and ccm of Gd2O3 (NCP) were 17.26 and 15.13s−1mM−1 and for Gd2O3 (deg) were 16.35, 14.62 s−1mM−1 respectively. Conclision: A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. No appreciable toxicity was observed with a Gd2O3 nanoparticles. Conclusion: Gadolinium‐Nanocomposite Polymer Emulsion is well characterised and potentialy useful positive contrast agent for magnetic resonance molecular imaging.

?Longitudinal Water Proton Relaxivities of Ultra Small 3d and 4f Transition Metal Oxide Nanoparticles

We report the longitudinal water proton relaxivities (r1) of several 3d and 3f transition metal oxide nanoparticles. These include ultrasmall iron oxide, manganese oxide, europium oxide, gadolinium oxide, and dysprosium oxide nanoparticles. The nanoparticles ranged from 1.0 to 3.0 nm in diameter. Ultrasmall metal oxide nanoparticles with metal ions of high and pure S-state electron magnetic moments showed high r1 relaxivities. The measured relaxivities indicate that ultrasmall gadolinium oxide nanoparticles with a high r1 relaxivity of 12.6 mM −1s−1 may be suitable for use as a sensitive T1 MRI contrast agent.