substances, was used to encapsulate a legion of nanoparticles simultaneously. The use of a cheap polymeric structure based on poly(maleic anhydride-alt-1-octadecene) (PMAO) conjugated with Jeffamine allowed to obtain nanoparticles with a size of about 100 nm. Multilayer polymer shell preserves the pronounced autocatalytic properties of CeO2 NPs and leaves oleic acid on their surface. It has been demonstrated that the synthesized nanoparticles do not exhibit a cytotoxic effect against NCTC L929 and MCF-7 cell cultures at concentrations ranging from 10- 6 to 10- 5 M. However, a moderate cytotoxic effect (below the IC50) is observed at a concentration of 10-4 M following a 72-hour co-incubation of nanoparticles with cells. It was determined that the polymer coating (PMAO-Jeffamine) does not hinder the catalytic functions of cerium, as evidenced by the model of oxidative stress induced by radiation, wherein the catalytic binding sites maintain accessibility. Furthermore, the selective redox activity of nanoparticles against cancerous and normal cells is observed, which can be utilized for biomedical purposes in the development of nanomaterials that enhance the effectiveness of radiation therapy.

In the original publication [...].

Background: The use of nanoradiosensitizers is a promising strategy for the precision enhancement of tumor tissue damage during radiotherapy. Methods: Here, we propose a novel biocompatible theranostic agent based on gadolinium fluoride doped with cerium and terbium (Gd0.7Ce0.2Tb0.1F3 NPs), which showed pronounced radiocatalytic activity when exposed to photon or proton beam irradiation, as well as remarkable MRI contrast ability. A scheme for the production of biocompatible colloidally stable Gd0.7Ce0.2Tb0.1F3 NPs was developed. Comprehensive physicochemical characterization of these NPs was carried out, including TEM, SEM, XRD, DLS, and EDX analyses, as well as UV–vis spectroscopy and MRI relaxation assays. Results: Cytotoxicity analysis of Gd0.7Ce0.2Tb0.1F3 NPs in vitro and in vivo revealed a high level of biocompatibility. It was shown that Gd0.7Ce0.2Tb0.1F3 NPs effectively accumulate in MCF-7 tumor cells. A study of their radiosensitizing activity demonstrated that the combined effect of Gd0.7Ce0.2Tb0.1F3 NPs and X-ray irradiation leads to a dose-dependent decrease in mitochondrial membrane potential, a sharp increase in the level of intracellular ROS, and the subsequent development of radiation-induced apoptosis. Conclusions: This outstanding radiosensitizing effect is explained by the radiocatalytic generation of reactive oxygen species by the nanoparticles, which goes beyond direct physical dose enhancement. It emphasizes the importance of evaluating the molecular mechanisms underlying the sensitizing effectiveness of potential nanoradiosensitizers before choosing conditions for their testing in in vivo models.

Cerium oxide nanoparticles (CeO2 NPs) show promise as radiosensitizers due to their capacity for selective enhancement of radiation damage in cancer cells. To advance their application, we developed a modular platform based on monodisperse CeO2 NPs (<= 9 nm), synthesized via a high-temperature organic-phase approach. We subsequently introduced a robust siloxane shell using a reverse microemulsion technique, achieving superior colloidal stability in aqueous media while preserving intrinsic radiosensitizing activity. This surface engineering enables facile covalent conjugation; we exemplify this by functionalizing the NPs with the fluorescent tracer fluorescein isothiocyanate (FITC). This strategy facilitated high-resolution fluorescence microscopy tracking of the intracellular CeO2 NP distribution without altering the NPs' physicochemical or radiobiological performance. Comprehensive MTT assays and gene expression analysis confirmed that the functionalized CeO2 NPs maintained their selective radiosensitization efficacy. This work establishes a robust synthetic and surface engineering strategy for creating traceable, biocompatible CeO2-based nanoradiosensitizers, significantly advancing their potential in image-guided cancer therapies.

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 gamma-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.

According to clinical assessment, 85–95

Curcumin is a natural bioactive substance with promising biomedical applications. However, the low solubility and stability of curcumin significantly limit its potential use. The development of nanoformulations of curcumin makes it possible to circumvent the above limitations. Cerium dioxide (CeO2, NDC) nanoparticles are a promising platform for curcumin binding. They are able to absorb curcumin on their surface, providing increased bioavailability and bioaccumulation. Moreover, NDC have unique enzyme-like properties that can be used for targeted delivery and controlled release of curcumin. Meanwhile, the potential cytotoxicity of such nanoformulations remains poorly understood. In this work, we synthesized the NDC-curcumin nanoconjugate and investigated the effect of excess curcumin on the cytotoxicity of this nanoformulation. Curcumin has been shown to bind to the surface of nanoparticles, forming a colloidally stable nanoconjugate. At the same time, excess curcumin formed a separate nanoscale fraction, which caused the statistically significant cytotoxicity of the nanoconjugate in relation to human keratinocytes (HaCaT), mesenchymal stem cells (hMSc) and fibroblasts (HF). These cell lines represent the cells that form skin, mucous membranes, and connective tissue, with which curcumin nanoformulations can interact through various methods of administration. IC50 values of curcumin and NDC-curcumin were 400 and 482 μM for HaCaT, 193 and 211 μM for hMSc, 266 and 304 μM for HF, respectively, after 72 h of coincubation. Consequently, NDC provided an increased biocompatibility of curcumin. Application of a rational design of curcumin nanoformulations can help to overcome possible limitations of its practical use due to its toxicity, enhancing its bioactivity.

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.

It is now well established that radiation-induced dermatitis is a complication in 85-95% of patients undergoing standard radiotherapy. Despite the fact that the pathogenesis of radiation dermatitis has been quite well studied, the factors influencing the severity of its course have been established, and its distinctive features compared to thermal and chemical burns have been demonstrated, the prevention and treatment of radiation dermatitis remains an unsolved problem, leading to a decrease in the quality of life of patients and various long-term complications. Today, hygienic procedures are recommended as preventive measures in clinical medicine, namely: daily keeping the skin clean, applying moisturizer, wearing clothes made of soft fabrics, avoiding temperature changes, and protecting from direct sunlight. In addition, a number of products are used to treat other forms of skin lesions – moisturizing and anti-inflammatory ointments and dressings. These procedures help to partially improve the patient’s quality of life; however, they do not have a therapeutic effect on the primary cellular and molecular causes of the development of radiation dermatitis. Currently, there are several potentially more effective treatment methods, such as targeted gene and cell therapy, bioactivators, a number of physical methods and nanocomposites. In our work, we considered modern achievements in the field of treatment of radiation dermatitis, paying special attention to the prospects for the use of nanobiotechnological drugs in connection with their extensive research for science and medicine.

Cerium dioxide nanoparticles (CeO2 NPs) are semiconductor metal oxide-based nanoparticles that possess the availability of “oxidation switch” on their surface. In response to external conditions, CeO2 NPs change the properties of surface Ce atoms, transforming into a core-shell structure. This unique property has been used in biomedical research and, in recent years, in analytics. However, there are very few works devoted to the use of CeO2 NPs in luminescence analysis. In this review, we summarize and critically discuss the use of CeO2 NPs in various luminescent signal detection methods as a luminescent nanolabel, luminescent nanosensor, luminescence quencher and nanozyme. Examples of CeO2 NPs utilizing as a nanosensor that provides high specificity are presented. At the same time, when used as a nanozyme, CeO2 NPs is very effective because they allow reversible enzyme-catalyzed reactions at physiological pH without the use of hydrogen peroxide and the enzyme itself. Further analytical applications and limitations of CeO2 NPs, which possess a set of unique properties, are also discussed.

Cerium oxide nanoparticles (CeO2 NPs), which have powerful antioxidant properties, are promising nanomaterials for the treatment of diseases associated with oxidative stress. The well-developed surface of CeO2 NPs makes them promising for use as a multifunctional system for various biomedical applications. This work demonstrates a simple approach that allows the direct formation of a molecular fluorophore on the surface of CeO2 NPs using a simple one-pot hydrothermal synthesis. Thus, we were able to synthesize CeO2 NPs of ultra-small size similar to 2 nm with a narrow distribution, highly stable fluorescence, and a quantum yield of similar to 62%. UV-visible transmission studies revealed that the resulting CeO2 NPs exhibited fast autogenerative catalytic reduction. In vitro results showed high biocompatibility of CeO2 NPs; their internalization occurs mainly in the region of cell nuclei. Thus, the resulting NPs have the necessary parameters and can be successfully used in biovisualization and therapy. Fluorophore-modified cerium oxide nanoparticles (CeO2 NPs), which have powerful antioxidant properties and high fluorescence intensity, are promising nanomaterials for the treatment of diseases associated with oxidative stress.

A BSTRACT Nanoscale cerium oxide (CeO2) is a bioavailable inorganic nanozyme exhibiting pronounced redox activity and capable of acting as a delivery system for bioactive compounds. We have synthesized and characterized novel CeO2 nanoparticles modified with pyrroloquinoline quinone (CeO2@PQQ). TEM analysis revealed the diameter of the CeO2@PQQ NPs to be approximately 4 nm, with a hydrodynamic diameter of 62 nm (DLS). Furthermore, the zeta potential was found to be - 38 mV (ELS), and FTIR analysis confirmed the adsorption of PQQ on the surface of CeO2 NPs. The results demonstrated that CeO2@PQQ NPs exhibited no cytotoxic effects on L929 cells within the concentration range of 0.1 - 10 mu M and did not adversely affect the mitochondrial function of the cells. It was demonstrated that CeO2@PQQ NPs exhibited protective effects against L929 cells when induced with oxidative stress (200 mu M H2O2), leading to preservation of cell mitochondrial potential levels up to 76 % of control and cell viability up to 78 % before and after incubation with CeO2@PQQ NPs. The results indicate that CeO2@PQQ NPs can be regarded as a novel hybrid nanosystem that exhibits mitochondrial-directed control of oxidative stress.

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.

Cerium(IV) oxide nanoparticles are promising agents for use in radiotherapy. The morphology of nanoparticles largely determines their effectiveness. This article presents the results of a study of the conditions for the deposition of cerium(IV) oxide nanoparticles, a detailed variation of the parameters of the syntheses, and assessment of their effectiveness from the point of view of the morphology of the resulting structures. The conditions for obtaining nanoparticles with optimal physicochemical properties, high stability, and reproducibility of synthesis have been selected.

Background and Objectives: In recent years, the attention of the scientific community has been attracted by cerium(IV) oxide nanoparticles (CeO2 NPs), which demonstrate great potential for use in biomedicine due to their unique biological properties such as antioxidant and antibacterial activity. The development of biomaterials that combine the properties of polymers and the unique characteristics of CeO2 NPs opens up new horizons for applications in biomedicine. A thin layer of polymers preserves the catalytic activity of cerium oxide without blocking the path of electronic charge transfer on the surface of nanoparticles. The relevance of the development of CeO2 NPs with a polymer shell lies in the fact that polymers can bind to various medicinal and bioactive substances, becoming drug carriers. This work describes the preparation of CeO2 NPs with various polymers in order to study how the composition and structure of the polymer affect the size and charge of the resulting nanoparticles. The variability of the properties of CeO2 NPs will make it possible to test them for the encapsulation of other substances, including drugs, in order to identify optimal polymers. Materials and Methods: Cerium(III) nitrate hexahydrate Ce(NO3)3 · 6H2O was used as a precursor for the synthesis of CeO2 NPs. Four different polymers were used for the syntheses: polyacrylic acid (PAA), polyethylene glycol (PEG), poly(isobutylene-alt-maleic anhydride) (PIMA). The synthesis was carried out in ammonium hydroxide (28–30%). CeO2 NPs with a polymer shell were obtained by chemical deposition. Polymer solutions were prepared and mixed with a 1 M solution of Ce(NO3)3. With continuous stirring, the mixture was added to the ammonium hydroxide solution, after which ethanol was added and left under stirring for 24 hours at room temperature. Results: We have presented the synthesis of cerium oxide nanoparticles in the presence of polymers of various compositions and molecular weights to study their effect on the structure and size of nanoparticles. During the synthesis, it has been revealed that the optimal concentration of cerium(III) nitrate for syntheses is 1 M. The influence of the environment on the possible agglomeration of nanoparticles during purification and further storage has been studied. The best media for storing and purifying nanoparticles are water and phosphate-buffered saline. The size and morphology of the resulting polymer-coated CeO2 NPs have been studied by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scattering (DLS). TEM images show nanocrystals measuring about 10 nm in all four samples. SEM images show the presence of particles with a size of about 20–30 nm in all four samples. DLS analysis has shown that the smallest particles were formed with polyacrylic acid and poly(isobutylene-alt-maleic anhydride). Conclusions: The results of the study have demonstrated that for the synthesis of CeO2 NPs with a polymer coating it is better to use PAA and PIMA polymers since smaller particles are formed. It has been found that it is optimal to use 1 M Ce(NO3)3 for syntheses, and the best media for purification and storage of CeO2 NPs are water and FSB.

Ionizing radiation-induced damage in cancer and normal cells leads to apoptosis and cell death, through the intracellular oxidative stress, DNA damage and disorders of their metabolism. Irradiation doses that do not lead to the death of tumor cells can result in the emergence of radioresistant clones of these cells due to the rearrangement of metabolism and the emergence of new mutations, including those in the genes responsible for DNA repair. The search for the substances capable of modulating the functioning of the tumor cell repair system is an urgent task. Here we analyzed the effect of cerium(III) fluoride nanoparticles (CeF3 NPs) on normal (human mesenchymal stem cells–hMSC) and cancer (MCF-7 line) human cells after X-ray radiation. CeF3 NPs effectively prevent the formation of hydrogen peroxide and hydroxyl radicals in an irradiated aqueous solution, showing pronounced antioxidant properties. CeF3 NPs are able to protect hMSC from radiation-induced proliferation arrest, increasing their viability and mitochondrial membrane potential, and, conversely, inducing the cell death of MCF-7 cancer cells, causing radiation-induced mitochondrial hyperpolarization. CeF3 NPs provided a significant decrease in the number of double-strand breaks (DSBs) in hMSC, while in MCF-7 cells the number of γ-H2AX foci dramatically increased in the presence of CeF3 4 h after irradiation. In the presence of CeF3 NPs, there was a tendency to modulate the expression of most analyzed genes associated with the development of intracellular oxidative stress, cell redox status and the DNA-repair system after X-ray irradiation. Cerium-containing nanoparticles are capable of providing selective protection of hMSC from radiation-induced injuries and are considered as a platform for the development of promising clinical radioprotectors.

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.

Purpose: To evaluate the effect of local proton irradiation at a dose of 30 Gy on Balb/c and C57BL/6 mice in terms of the degree and dynamics of radiation-induced skin damage formation, changes in body weight and peripheral blood elements count. Material and methods: Experiments were performed on non-depilated male mice aged 7‒8 weeks from two strains: Balb/c and C57BL/6 (n=15). Local irradiation of the skin was carried out on the dorsal side of the animals using a scanning proton beam at an extended Bragg peak in the proton therapy complex «Prometheus» of the LPI Physico-technical Centre (Protvino) at a dose of 30 Gy with a proton energy of 87.8 MeV. During the irradiation session, animals were subjected to intraperitoneal anesthesia using a combination of Zoletil 100 (Virbac, France) and Xyla (Interchemie, Netherlands) in a previously determined ratio 1:3 (20‒40 mg/kg). Photographic documentation of radiation-induced skin damage was performed weekly for 70 days. Animals were examined daily for clinical manifestations of radiation-induced skin damage formation according to the RTOG international scale for 21 days following irradiation. The body weight dynamics of mice were evaluated one day before irradiation and then weekly for 70 days. Blood samples were collected from the tail vein by cutting the tip of the tail and analyzed using a DH36 Vet hematology analyzer (Dymind, China) one day before irradiation, one day and three days after irradiation, and weekly thereafter for 70 days. Experimental data were presented as mean ± standard deviation (M ± SD). Results: In this study, the impact of a single local exposure to proton radiation at a dose of 30 Gy on the degree and dynamics of radiation-induced skin damage formation was evaluated. It was demonstrated that Balb/c mice exhibited a higher frequency and degree of radiation-induced skin damage formation compared to the C57BL/6 mice. Analysis of body weight in mice after radiation exposure revealed no significant decrease in either mouse strain. A comparative analysis of the number of platelets, erythrocytes and hemoglobin concentration in both mouse strains did not reveal any changes, while a tendency towards a decrease in the number of leukocytes, lymphocytes, and granulocytes was observed in the irradiated Balb/c mice group compared to the control group. Conversely, in irradiated C57BL/6 mice, the number of lymphocytes was higher compared to control animals. Conclusion: In this study, Balb/c mice exhibited higher radiosensitivity compared to C57BL mice in response to a single local proton irradiation at a dose of 30 Gy.