Ultrasmall cerium oxide nanoparticles as highly sensitive X-ray contrast agents and their antioxidant effect

Owing to their theranostic properties, cerium oxide (CeO₂) nanoparticles have attracted considerable attention for their key applications in nanomedicine. In this study, ultrasmall CeO₂ nanoparticles (particle diameter = 1-3 nm) as X-ray contrast agents with an antioxidant effect were investigated for the first time. The nanoparticles were coated with hydrophilic and biocompatible poly(acrylic acid) (PAA) and poly(acrylic acid-co-maleic acid) (PAAMA) to ensure satisfactory colloidal stability in aqueous media and low cellular toxicity. The synthesized nanoparticles were characterized using high-resolution transmission electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, cell viability assay, photoluminescence spectroscopy, and X-ray computed tomography (CT). Their potential as X-ray contrast agents was demonstrated by measuring phantom images and in vivo CT images in mice injected intravenously and intraperitoneally. The X-ray attenuation of these nanoparticles was greater than that of the commercial X-ray contrast agent Ultravist and those of larger CeO₂ nanoparticles reported previously. In addition, they exhibited an antioxidant effect for the removal of hydrogen peroxide. The results confirmed that the PAA- and PAAMA-coated ultrasmall CeO₂ nanoparticles demonstrate potential as highly sensitive radioprotective or theranostic X-ray contrast agents.