Cerium Oxide Nanoparticles with Entrapped Gadolinium for High T(1) Relaxivity and ROS-Scavenging Purposes

[Image: see text] 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 Ce(3+) sites and oxygen vacancies at the surface plays a critical role in providing the antioxidant properties. The characterization of radial distribution of Ce(3+) and Ce(4+) oxidation states indicated a higher concentration of Ce(3+) 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.