Radiocatalytic properties of gadolinium-containing cerium oxide nanoparticles and their sensitizing effects on 3D-tumor cell spheroids

Gadolinium (Gd)-based complexes are widely used in magnetic resonance imaging (MRI), however, their safety remains controversial. A key risk factor is the accumulation of gadolinium ions in healthy tissues upon repeated administration of these agents. Thus, there is an urgent need to develop new safe approaches for MRI imaging. One promising strategy involves nanoparticle-based formulations, which can minimize gadolinium ion release by retaining them within the crystal lattice. In this study, we developed cerium oxide nanoparticles doped with 10% and 20% (mol.) gadolinium (Ce0.8Gd0.1O2-х and Ce0.8Gd0.2O2-х, respectively). Their radiosensitizing properties were evaluated in a cell-free system and on 3D tumor cell spheroids. The nanoparticles containing 10% gadolinium exhibited pronounced radiocatalytic activity, whereas increasing the gadolinium content to 20% significantly reduced their radiosensitizing effects. pH-dependent radiation-induced activity of the nanoparticles was demon-strated. The most prominent reactive oxygen species (ROS) generation was observed at pH 6.5, while at pH 7.4, ROS production was notably lower. The combined action of Ce0.8Gd0.2O2- and X-ray irradiation suppressed the migratory activity of 4T1 and EMT6/P tumor cells in 3D spheroids. This effect may be attributed to enhanced ROS generation in the presence of the nanoparticles. The developed gadolinium-containing cerium oxide nanoparticles represent a promising theranostic agent for tumor diseases.