Gadolinium chelates are employed worldwide today as clinical contrast agents for magnetic resonance imaging. Until now, the commonly used linear contrast agents based on the rare-earth element gadolinium have been considered safe and well-tolerated. Recently, concerns regarding this type of contrast agent have been reported, which is why there is an urgent need to develop the next generation of stable contrast agents with enhanced spin-lattice relaxation, as measured by improved T-1 relaxivity at lower doses. Here, we show that by the integration of gadolinium ions in cerium oxide nanoparticles, a stable crystalline 5 nm sized nanoparticulate system with a homogeneous gadolinium ion distribution is obtained. These cerium oxide nanoparticles with entrapped gadolinium deliver strong T-1 relaxivity per gadolinium ion (T-1 relaxivity, r(1) = 12.0 mM(-1) s(-1)) with the potential to act as scavengers of reactive oxygen species (ROS). The presence of Ce3+ sites and oxygen vacancies at the surface plays a critical role in providing the antioxidant properties. The characterization of radial distribution of Ce3+ and Ce4+ oxidation states indicated a higher concentration of Ce3+ at the nanoparticle surfaces. Additionally, we investigated the ROS-scavenging capabilities of pure gadolinium-containing cerium oxide nanoparticles by bioluminescent imaging in vivo, where inhibitory effects on ROS activity are shown.

Cerium oxide nanoparticles with integrated gadolinium have been proved to be useful as contrast agents in magnetic resonance imaging. Of question is their performance in dual-energy computed tomography. The aims of this work are to determine (1) the relation between the computed tomography number and the concentration of the I, Gd or Ce contrast agent and (2) under what conditions it is possible to resolve the type of contrast agent. Hounsfield values of iodoacetic acid, gadolinium acetate and cerium acetate dissolved in water at molar concentrations of 10, 50 and 100 mM were measured in a water phantom using the Siemens SOMATOM Definition Force scanner; gadolinium- and cerium acetate were used as substitutes for the gadolinium-integrated cerium oxide nanoparticles. The relation between the molar concentration of the I, Gd or Ce contrast agent and the Hounsfield value was linear. Concentrations had to be sufficiently high to resolve the contrast agents.

Chrome-based anodization and sealing combined is a cost-effective solution for developing good corrosion protective coatings on aluminum (Al) and its alloys. The toxicity of hexavalent chromium, however, requires new, sustainable, environmentally friendly, and efficient chromate-free sealing procedures. Herein, a combination of cerium (Ce) sealing and hydrothermal sealing (HTS) is employed to improve the corrosion resistance of the commonly used alloy AA2024-T3 anodized by tartaric sulfuric acid (TSA). The morphologies and components of the resulting surfaces are systematically studied. Characterization technologies such as SEM, TEM, EDX, XRD, and XPS demonstrate the in-situ growth of Ce oxide nanoparticles all through the porous structures of the anodic coating and closing of the pores by additional HTS treatment. The results from the standardized corrosion test (ASTM B895) demonstrate an improved corrosion resistance obtained by the utilized chrome-free process.

Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle-protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both 'danger signals', verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations.

Neutrophil granulocytes are the most abundant white blood cells in mammals and vital components of the immune system. They are involved in the early phase of inflammation and in generation of reactive oxygen species. These rapid cell-signaling communicative processes are performed in the time frame of minutes. In this work, the activity and the response of neutrophil granulocytes are monitored when triggered by cerium-oxide based nanoparticles, using capacitive sensors based on Lab-on-a-chip technology. The chip is designed to monitor activation processes of cells during nanoparticle exposure, which is for the first time recorded on-line as alteration of the capacitance. The complementary metal oxide semiconductor engineering chip design is combined with low temperature co-fired ceramic, LTCC, packaging technology. The method is label free and gently measures cells on top of an insulating surface in a weak electromagnetic field, as compared to commonly used four-point probes and impedance spectroscopy electric measurements where electrodes are in direct contact with the cells. In summary, this label free method is used to measure oxidative stress of neutrophil granulocytes in real time, minute by minute and visualize the difference in moderate and high cellular workload during exposure of external triggers. It clearly shows the capability of this method to detect cell response during exposure of external triggers. In this way, an informationally dense non-invasive method is obtained, to monitor cells at work.

The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue- and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce 3+ and Ce 4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on a b initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3–5 nm in size, have r 1 -relaxivities between 7–13 mM −1 s −1 and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.

Reactive oxygen species (ROS) regulating the release of free zinc ions (Zn2+) in cellular lysosome is closely related to various pathways of cellular signal transduction, such as inflammation and oxidative stress. Directly visualizing Zn2+ release in lysosome is essential for in-depth understanding these physiological processes, and is still an atelic challenge. In this work, we successfully fabricate a lysosome-specific Zn2+ fluorescent probe and achieve the visualization of ROS-induced Zn2+ release in lysosome of inflammatory cells. The as-prepared probe combines a green fluorophore, an ionophore with five-dentate sites, and a morpholine as the lysosome-specific localization moiety. The fluorescence of the fluorophore in the free probe is suppressed by a photoinduced electron transfer (PET) process from nitrogen atoms in the ionophore. Upon the addition of Zn2+, the fluorescence can be promoted immediately, achieving the real-time detection. Meanwhile, the probe is sensitive and selective to Zn2+, which provides the capability to detect low-concentration of free Zn2+ in lysosomes. Accordingly, the Zn2+ release was clearly observed in lysosome with the increase of ROS levels when the inflammation occurred in living cells. (c) 2018 Published by Elsevier B.V.