Ionizing radiation leads to the development of oxidative stress and damage to biologically important macromolecules (DNA, mitochondria, etc.), which in turn lead to cell death. In the case of radiotherapy, both cancer cells and normal cells are damaged. In this regard, the development of new selective antioxidants is relevant. In this study, we first investigated the redox activity of cerium oxide-pyrroloquinoline quinone nanoparticles (CeO₂@PQQ NPs) and their cytotoxic effects on normal (mouse fibroblasts, L929) and cancer (mouse adenocarcinoma, EMT6/P) cell cultures. Furthermore, the biological activity of CeO₂@PQQ NPs was evaluated in comparison with that of CeO₂ NPs and PQQ. The nanoparticles demonstrated pH-dependent reductions in the content of hydrogen peroxide after X-ray exposure. Our findings indicate that viability of EMT6/P cells was more adversely affected by CeO₂@PQQ NPs at lower concentrations (0.1 μM) compared to L929. Following X-ray irradiation at a dose of 5 Gy, significant changes in mitochondrial potential (by 29%) and decreased glutathione levels (by 32%) were also observed in EMT6/P culture following irradiation and incubation with CeO₂@PQQ NPs. Furthermore, EMT6/P exhibited a 2.5-fold increase in micronuclei and a 2-fold reduction in survival fraction compared to L929. It is hypothesized that CeO₂@PQQ NPs may exhibit selective cytotoxicity and radiosensitizing properties against EMT6/P cancer cells. The findings suggest that CeO₂@PQQ NPs may have potential as a selective redox-active antioxidant/pro-oxidant in response to X-ray radiation.

X-ray-induced photodynamic therapy (X-PDT) represents a promising new method of cancer treatment. A novel type of nanoscintillator based on cerium fluoride (CeF₃) nanoparticles (NPs) modified with flavin mononucleotide (FMN) has been proposed. A method for synthesizing CeF₃-FMN NPs has been developed, enabling the production of colloidal, spherical NPs with an approximate diameter of 100 nm, low polydispersity, and a high fluorescence quantum yield of 0.42. It has been demonstrated that CeF₃-FMN NPs exhibit pH-dependent radiation-induced redox activity when exposed to X-rays. This activity results in the generation of reactive oxygen species, which is associated with the scintillation properties of cerium and the transfer of electrons to FMN. The synthesized NPs have been demonstrated to exhibit minimal cytotoxicity towards normal cells (NCTC L929 fibroblasts) but are more toxic to tumor cells (epidermoid carcinoma A431). Concurrently, the synthesized NPs (CeF₃ and CeF₃-FMN NPs) demonstrate a pronounced selective radiosensitizing effect on tumor cells at concentrations of 10⁻⁷ and 10⁻³ M, resulting in a significant reduction in their clonogenic activity, increasing radiosensitivity for cancer cells by 1.9 times following X-ray irradiation at a dose of 3 to 6 Gy. In the context of normal cells, these nanoparticles serve the function of antioxidants, maintaining a high level of clonogenic activity. Functional nanoscintillators on the basis of cerium fluoride can be used as part of the latest technologies for the treatment of tumors within the framework of X-PDT.

Radiation dermatitis (RD) is one of the most common side effects of radiation therapy. However, to date, there is a lack of both specific treatments for RD and validated experimental animal models with the use of various sources of ionizing radiation (IR) applied in clinical practice. The aim of this study was to develop and validate a model of acute RD induced using proton radiation in mice. Acute RD (Grade 2–4) was obtained with doses of 30, 40, and 50 Gy, either with or without depilation. The developed model of RD was characterized by typical histological changes in the skin after irradiation. Moreover, the depilation contributed to a skin histology alteration of the irradiated mice. The assessment of animal vital signs indicated that there was no effect of proton irradiation on the well-being or general condition of the animals. This model can be used to develop effective therapeutic agents and study the pathogenesis of radiation-induced skin toxicity, including that caused by proton irradiation.

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.