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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-Gd(2)O(3)) 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)-Gd(2)O(3) nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd(2)O(3) nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) 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 Gd(2)O(3). 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 size distribution and magnetic properties of ultra-small gadolinium oxide crystals (US-Gd 2 O 3 ) were studied, and the impact of polyethylene glycol capping on the relaxivity constants (r 1 , r 2 ) and signal intensity with this contrast agent was investigated. Size distribution and magnetic properties of US-Gd 2 O 3 nanocrystals were measured with a TEM and PPMS magnetometer. For relaxation studies, diethylene glycol (DEG)-capped US-Gd 2 O 3 nanocrystals were reacted with PEG-silane (MW 5000). Suspensions were adequately dialyzed in water to eliminate traces of Gd 3+ and surfactants. The particle hydrodynamic radius was measured with dynamic light scattering (DLS) and the proton relaxation times were measured with a 1.5 T MRI scanner. Parallel studies were performed with DEG-Gd 2 O 3 and PEG-silane-SPGO (Gd 2 O 3 , < 40 nm diameter). The small and narrow size distribution of US-Gd 2 O 3 was confirmed with TEM (∼3nm)andDLS.PEG-silane-US-Gd 2 O 3 relaxation parameters were twice as high as for Gd-DTPA and the r 2 /r 1 ratio was 1.4. PEG-silane-SPGO gave low r 1 relaxivities and high r 2 /r 1 ratios, less compatible with positive contrast agent requirements. Higher r 1 were obtained with PEG-silane in comparison to DEG-Gd 2 O 3 . Treatment of DEG-US-Gd 2 O 3 with PEG-silane provides enhanced relaxivity while preventing aggregation of the oxide cores. This study confirms that PEG-covered Gd 2 O 3 nanoparticles can be used for positively contrasted MR applications requiring stability, biocompatible coatings and nanocrystal functionalization.

Ultrasmall gadolinium oxide nanoparticles doped with terbium ions were synthesized by the polyol route and characterized as a potentially bifunctional material with both fluorescent and magnetic contrast agent properties. The structural, optical, and magnetic properties of the organic-acid-capped and PEGylated Gd 2 O 3 :Tb 3+ nanocrystals were studied by HR-TEM, XPS, EDX, IR, PL, and SQUID. The luminescent/fluorescent property of the particles is attributable to the Tb 3+ ion located on the crystal lattice of the Gd 2 O 3 host. The paramagnetic behavior of the particles is discussed. Pilot studies investigating the capability of the nanoparticles for fluorescent labeling of living cells and as a MRI contrast agent were also performed. Cells of two cell lines (THP-1 cells and fibroblasts) were incubated with the particles, and intracellular particle distribution was visualized by confocal microscopy. The MRI relaxivity of the PEGylated nanoparticles in water at low Gd concentration was assessed showing a higher T 1 relaxation rate compared to conventional Gd-DTPA chelates and comparable to that of undoped Gd 2 O 3 nanoparticles.

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.

The knowledge of how to control the pore size and morphology of separated mesoporous silica particles is crucial for optimizing their performance in applications, such as molecular sieves and drug delivery systems. In this work, we have systematically studied the effects of various synthesis parameters to gain a deeper understanding of how particle morphologies can be altered. It was found that the morphology for isolated particles of SBA-15 type, with unusually short and wide pores, could be altered from rods to platelets by variations in the NH4F concentration. The pore length is nearly constant (~300 nm) for the different morphologies, but the particle width is increasing from 200 nm to >3 μm when decreasing the amount of NH4F, and the pore size can be tuned between 10 and 13 nm. Furthermore, other synthesis parameters such as heptane concentration, pH, silica precursor, and additions of ions have also been studied. The trend regarding particle width is independent of heptane concentration, at the same time as heptane increases the particle length up to a plateau value of ~500 nm. In all, parameters controlling particle width, length, and pore size have been separated in order to evaluate their function in the particle formation. Additionally, it was found that the formation time of the particles is strongly affected by the fluoride ion concentration, and a mechanism for particle formation for this system, where micelles transform from a foam, to multilamellar vesicles, and finally to cylindrical micelles, is suggested.

In all kinds of gadolinium based contrast agents, the presence of free gadolinium ions have to be avoided due to the cytotoxicity. The conventional way of producing a gadolinium based contrast agent is to form a chelate, i.e. stabilizing the metal ion using a chelating agent (for example DTPA or DOTA) but recently nanoparticles is an initial step towards biocompatible and directed nanoparticles.The main focus is on a material that in the nearby future will be the core of an The experimental results are supported by theoretical modeling studies.Theoretical IR spectra of three different Gd acetate complexes are presented as well as calculated NEXAFS spectra of one of the Gd acetate complexes and an isolated acetate group. These calculations were performed to elucidate the molecular capping of the synthesized particles. 5 EXPERIMENTAL DETAILS ChemicalsAll chemicals were used as received. Gadolinium(III) acetate hydrate (SigmaAldrich, 99.9 %), tetramethylammonium hydroxide (Sigma-Aldrich, >97 % ), ethyl acetate (Fisher Scientific, 99.99 %), dimethyl sulfoxide (Merck, 99.9 %), ammonium acetate (Merck, >96%), ethanol (Kemetyl, 99.5 %). For preparation of water based solutions, Milli-Q water (ρ > 18.2 MΩ) was used. A commercial gadolinium oxide nanopowder (Aldrich, < 100 nm, 99.8 %) was used as a reference. Preparation of Gd 2 O 3 nanoparticlesThe preparation of Gd 2 O 3 nanoparticles was based on a method previously used for producing nanocrystalline ZnO (Schwartz et al. 2003). As Zn 2+ is divalent and Ethyl acetate was added and the mixture was centrifuge washed (3500 rpm) at least three times with ethyl acetate before it was diluted in deionized water. A total amount of 0.28 g ammonium acetate was added to one whole batch to increase the water solubility. Powder samples were air dried. The yield of the sample is dependent on the washing procedure. The gadolinium content after three times of centrifuge washing with ethyl acetate is roughly 60-65 % of the initial amount added in the synthesis.6 Instrumentation X-ray diffraction XRD measurements were carried out with a Philips XRD powder diffractometer using Cu Kα radiation (λ = 1.5418 Å, 40kV, 40 mA). The 2θ step-size was 0.025° and the time per step 4 s. Air dried powder samples were used in the preparation.High-resolution transmission electron microscopy TEM measurements were performed on a FEI Tecnai G 2 electron microscope operated at 200 kV. Sample preparation was done by letting 1-2 drops of Gd 2 O 3 in water dry on an amorphous carbon-covered copper grid.Dynamic light scattering DLS measurements were carried out on an ALV/DLS/SLS-5022F system from ALV-GmbH, Langen Germany, using a HeNe laser at 632.8 nm with 22 mW output power. Prior to the measurements, the samples were temperature stabilized in a thermostat bath at 22.1 °C for at least 10 minutes. The scattering angle was 90°. 15 Gd 2 O 3 samples dispersed in MilliQ water were studied in DLS, and the long term stability of the suspensions were studied by repeated measurements during a period of 6 weeks.ζ Pot...

Electrochemical synthesis and physical characterization of ZnO nanoparticles functionalized with four different organic acids, three aromatic (benzoic, nicotinic, and trans-cinnamic acid) and one nonaromatic (formic acid), are reported. The functionalized nanoparticles have been characterized by X-ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, UV-vis, and photoluminescence spectroscopy. The adsorption of the organic acids at ZnO nanoparticles was further analyzed and interpreted using quantum-chemical density-functional theory computations. Successful functionalization of the nanoparticles was confirmed experimentally by the measured splitting of the carboxylic group stretching vibrations as well as by the N(1s) and C(1s) peaks from XPS. From a comparison between computed and experimental IR spectra, a bridging mode adsorption geometry was inferred. PL spectra exhibited a remarkably stronger near band edge emission for nanoparticles functionalized with formic acid as compared to the larger aromatic acids. From the quantum-chemical computations, this was interpreted to be due to the absence of aromatic adsorbate or surface states in the band gap of ZnO, caused by the formation of a complete monolayer of HCOOH. In the UV-vis spectra, strong charge-transfer transitions were observed.