CeO2 Nanoparticles Initiate Selective Radiation-Induced Death of Cancer Cells through Redox, Cell Cycle, and DNA Repair Disruptions

Citrate-stabilized cerium oxide nanoparticles (CeO₂ NPs) with ultrasmall size (2–4 nm) were synthesized and comprehensively characterized, demonstrating high colloidal stability and favorable redox properties. Their radioprotective and radiosensitizing potential was evaluated in aqueous systems and in vitro using human mesenchymal stem cells (hMSCs) and MCF-7 breast cancer cells. CeO₂ NPs exhibited concentration-dependent catalytic activity, efficiently scavenging hydrogen peroxide and hydroxyl radicals under X-ray irradiation. In hMSCs, CeO₂ NPs promoted proliferation, reduced apoptosis, and attenuated DNA double-strand breaks, thereby conferring radioprotection. In contrast, in MCF-7 cells, CeO₂ NPs enhanced ROS accumulation, disrupted cell-cycle checkpoints, increased γ-H2AX foci, and sensitized cells to radiation-induced apoptosis. Gene expression profiling revealed differential regulation of oxidative stress and apoptosis pathways consistent with selective protection of normal cells and radiosensitization of cancer cells. These findings highlight the dual redox-dependent activity of CeO₂ NPs and support their potential application as nanomaterials for radioprotection and radiosensitization.