There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd₂O₃) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd₂O₃-labeled cells have shorter T₁ and T₂ relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd₂O₃ nanoparticles can be used as a positive contrast agent for cell labeling. The r₁ for cell samples was 4.1 and 3.6 s^-1 mm^-1 for cell culture medium. The r₂ was 17.4 and 12.9 s^-1 mm^-1, respectively. For r₁, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (p_r1 = 0.36), but r₂ was significantly different for the two different series (p_r2 = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd₂O₃ nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells.

Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study, we report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in MRI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3−5 nm) gadolinium oxide (DEG-Gd₂O₃) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd₂O₃ nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd₂O₃ nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r₁ and r₂ values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd₂O₃. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is, an extremely high MR signal at the cellular and molecular level.

The performance of a magnetic resonance imaging contrast agent (CA) depends on several factors, including the relaxation times of the unpaired electrons in the CA. The electron spin relaxation time may be a key factor for the performance of new CAs, such as nanosized Gd2O3 particles. The aim of this work is, therefore, to study changes in the magnetic susceptibility and the electron spin relaxation time of paramagnetic Gd2O3 nanoparticles diluted with increasing amounts of diamagnetic Y2O3. Nanoparticles of (GdxY1-x)2O3 (0 e x e 1) were prepared by the combustion method and thoroughly characterized (by X-ray di.raction, transmission electron microscopy, thermogravimetry coupled with mass spectroscopy, photoelectron spectroscopy, Fourier transform infrared spectroscopy, and magnetic susceptibility measurements). Changes in the electron spin relaxation time were estimated by observations of the signal line width in electron paramagnetic resonance spectroscopy, and it was found that the line width was dependent on the concentration of yttrium, indicating that diamagnetic Y2O3 may increase the electron spin relaxation time of Gd2O3 nanoparticles.

Chelated gadolinium ions, e. g., GdDTPA, are today used clinically as contrast agents for magnetic resonance imaging (MRI). An attractive alternative contrast agent is composed of gadolinium oxide nanoparticles as they have shown to provide enhanced contrast and, in principle, more straightforward molecular capping possibilities. In this study, we report a new, simple, and polyol-free way of synthesizing 4-5-nm-sized Gd2O3 nanoparticles at room temperature, with high stability and water solubility. The nanoparticles induce high-proton relaxivity compared to Gd-DTPA showing r(1) and r(2) values almost as high as those for free Gd3+ ions in water. The Gd2O3 nanoparticles are capped with acetate and carbonate groups, as shown with infrared spectroscopy, near-edge X-ray absorption spectroscopy, X-ray photoelectron spectroscopy and combined thermogravimetric and mass spectroscopy analysis. Interpretation of infrared spectroscopy data is corroborated by extensive quantum chemical calculations. This nanomaterial is easily prepared and has promising properties to function as a core in a future contrast agent for MRI.

Water-dispersible and luminescent gadolinium oxide (GO) nanoparticles (NPs) were designed and synthesized for potential dual-modal biological imaging. They were obtained by capping gadolinium oxide nanoparticles with a fluorescent glycol-based conjugated carboxylate (HL). The obtained nanoparticles (GO-L) show long-term colloidal stability and intense blue fluorescence. In addition, L can sensitize the luminescence of europium(III) through the so-called antenna effect. Thus, to extend the spectral ranges of emission, europium was introduced into L-modified gadolinium oxide nanoparticles. The obtained Eu-III-doped particles (Eu:GO-L) can provide visible red emission, which is more intensive than that without L capping. The average diameter of the monodisperse modified oxide cores is about 4nm. The average hydrodynamic diameter of the L-modified nanoparticles was estimated to be about 13nm. The nanoparticles show effective longitudinal water proton relaxivity. The relaxivity values obtained for GO-L and Eu:GO-L were r(1)=6.4 and 6.3s(-1)mM(-1) with r(2)/r(1) ratios close to unity at 1.4T. Longitudinal proton relaxivities of these nanoparticles are higher than those of positive contrast agents based on gadolinium complexes such as Gd-DOTA, which are commonly used for clinical magnetic resonance imaging. Moreover, these particles are suitable for cellular imaging and show good biocompatibility.

Gadolinium decorated ZnO nanoparticles simultaneously possess both fluorescent and MR enhancement properties. These ZnO nanoparticles are crystalline and shielded by an amorphous gadolinium acetate matrix. Interestingly, the Gd-acetate decoration enhances the fluorescence emission of the ZnO nanoparticles. The quantum yield does increase for samples with high Gd/Zn relative ratios and these samples do also show a higher colloidal stability.

In addition, these nanoparticles show an enhanced relaxivity value per Gd atom (r₁19.9mM¹s^-1) compared to results earlier reported both on Gd alloyed ZnO nanoparticles and pure Gd2O3 nanoparticles. This improvement is considered to be due to the close proximity of Gd atoms and surrounding water molecules. A comprehensive study of the quantum yield and the relaxivity, as a function of composition, enable us to identify the ultimate design/composition of gadolinium decorated ZnO nanoparticles for optimum fluorescence and MR enhancement properties.

Sub 5 nm sized manganese oxide nanoparticles; MnOx (1 ≤ x ≤ 2), were synthesized via a short time room temperature synthesis route. The nanoparticles are crystalline, spherically shaped and in the size range of 2-4 nm as shown by transmission electron microscopy studies. Selected area electron diffraction patterns were collected and their appearance indicated that the nanoparticle cores are composed of MnO. Also, co-existence of the (II) and (III) oxidation states at the nanoparticle surface was verified by results achieved from infrared spectroscopy and X-ray photoelectron spectroscopy. These measurements also supported presence of a minor amount of acetate groups as well as a negligible fraction of carbonate groups at the nanoparticle surfaces. The interpretation of the IR spectra was confirmed by quantum chemical calculations using the high spin manganese nanoparticle Mn₁₂O₁₂(OAc)₁₆(H₂O)₄, as a model system for the MnO_x nanoparticle surface. Bulk MnO and Mn2O3 are known to be antiferromagnetic. The magnetic properties are however somewhat dependent of the crystallite size and changes when scaling down to the nanoregion. The MnO_x (1 ≤ x ≤ 2) nanoparticles investigated in this work show a superparamagnetic behavior with a blocking temperature of approximately 12 K proven by means of SQUID measurements. The relaxivities of the nanoparticles and the Mn(OAc)2 precursors were studied with a bench top NMR analyzer verifying nanoparticle r1 and r2 of 0.5 and 6 mMs^-1 respectively. The r1 relaxivity is lower than what is earlier reported for Gd based contrast agent, but improvements are expected by further surface modification, due to increased rotational time and higher water dispersability.