Nanoceria Inhibit the Cell Migration from 3D Tumor Spheroid Formed From 4T1 Human Breast Cancer Cells

The use of various nanoformulations for cancer radiotherapy has great potential due to their increased effectiveness and safety. At the stage of preclinical evaluation of such nanoformulations in vitro, they are tested on monolayers of tumor cell cultures, which is an unrealistic representation of tumors in vivo, which leads to an inaccurate selection of suitable drugs. To solve this problem, 3D cellular spheroids are becoming an additional tool for confirming the effectiveness of new therapeutic nanoformulations. Here we show the possibility of using citrate-stabilized cerium oxide nanoparticles (nanoceria, CeO2 NPs) as a nanoradiosensitizer in an experimental 3D model of tumor spheroids formed from 4T1 human breast cancer cells. It has been shown that ultra-small size (about 1-2 nm) CeO2 NPs have pH-sensitive radiocatalytic activity, increasing the generation of ROS under irradiation conditions. It has been shown that preloading of CeO2 NPs into a cellular spheroid at a micromolar concentrations does not adversely affect the rate of spheroid formation and its final size. However, such preloading has a pronounced inhibitory effect on the rate of cell migration from the spheroid after X-ray irradiation and also reduces their clonogenic activity. Thus, CeO2 NPs can be considered as a promising nanoradiosensitizer for radiotherapy of tumors.