Non-stoichiometric nano-CeO2 shows peroxidase activity both in flask and in vitro; under Fenton-like conditions the effect is reversed: pro-oxidant in flask and protective in vitro. The addition of nano-Pt to CeO2 enhances the effects in all cases.

Viral infections account for a large proportion of the total number of fatal diseases and require close attention from the international public health community. The COVID-19 pandemic has highlighted problems in medicine and healthcare related to the search for effective substances for the prevention, diagnosis and treatment of viral infections. According to many scientific studies, cerium species are very promising biomedical materials for combatting viral infections and have shown encouraging results in killing viruses on non-living objects, reducing viral load both in vitro and in vivo, relieving symptoms and reducing the consequences of viral diseases. This review critically examines the current level of knowledge on cerium species and their practical applications, with a focus on CeO2 nanoparticles (CeNPs). This review also seeks to assess the prospects for their development and use in antiviral theranostics.

Cerium oxide nanoparticles (CeNPs) show great promise in biomedical applications such as theranostics of various diseases, including viral infection. In this work, we synthesized bare, histidine-and glycinefunctionalized CeNPs sols and characterized them using DLS, TEM and AFM imaging, synchrotron radiation based techniques (XPS, RPES, NEXAFS). Toxicity and antiviral activity of CeNPs were evaluated using two cell lines (mouse fibroblasts L929 and monkey kidney epithelial cells MA-104) and three types of enveloped viruses (vesicular stomatitis virus VSV, bovine beta coronavirus BCoV-1 and herpes simplex virus HSV-1/2) in vitro. The obtained data indicate the absence of toxic effects up to the maximum concentrations of CeNPs (0.05 M), wherein the growth-stimulating action was shown for all samples. A dose-dependent antiviral effect of CeNPs was demonstrated. The effect was the most pronounced for VSV, which enters the cell by endocytosis and triggers fusion at low pH. The histidine-functionalized CeNPs were the most stable and had enhanced ability to reduce the viral cytopathic effect; their therapeutic index for VSV was >50 to 1000 depending on cell type. An attempt was made to explain the observed phenomena from the point of view of the physics of the synthesized particles and the biology of the virus-cell interaction.

Novel radioprotectors are strongly demanded due to their numerous applications in radiobiology and biomedicine, e.g., for facilitating the remedy after cancer radiotherapy. Currently, cerium-containing nanomaterials are regarded as promising inorganic radioprotectors due to their unrivaled antioxidant activity based on their ability to mimic the action of natural redox enzymes like catalase and superoxide dismutase and to neutralize reactive oxygen species (ROS), which are by far the main damaging factors of ionizing radiation. The freshwater planarian flatworms are considered a promising system for testing new radioprotectors, due to the high regenerative potential of these species and an excessive amount of proliferating stem cells (neoblasts) in their bodies. Using planarian Schmidtea mediterranea, we tested CeO2 nanoparticles, well known for their antioxidant activity, along with much less studied CeF3 nanoparticles, for their radioprotective potential. In addition, both CeO2 and CeF3 nanoparticles improve planarian head blastema regeneration after ionizing irradiation by enhancing blastema growth, increasing the number of mitoses and neoblasts’ survival, and modulating the expression of genes responsible for the proliferation and differentiation of neoblasts. The CeO2 nanoparticles’ action stems directly from their redox activity as ROS scavengers, while the CeF3 nanoparticles’ action is mediated by overexpression of “wound-induced genes” and neoblast- and stem cell-regulating genes.

The effect of various concentrations (1 μM – 100 mM) of citrate-stabilized cerium dioxide nanoparticles or cerium ions (3+) on the biomass production of two species of unicellular green algae Desmodesmus armatus (Chod.) Hegew and Acutodesmus dimorphus (Turpin) Tsarenko was studied, the amount of chlorophyll, proteins and lipids in the algae biomass was determined. It was shown that at the concentrations of 0.01 M to 0.1 M nanoparticles and cerium salt have pronounced toxic effects on the algal cultures, manifested by a sharp increase in the level of lipids in the biomass combined with the decrease in chlorophyll and protein. At lower concentrations, cerium dioxide nanoparticles stimulate algae biomass accumulation, probably due to a change in key metabolic pathways, accompanied by an increase in the accumulation of carbohydrates in the biomass. For cerium salt, these effects are less pronounced. Thus, depending on the concentration of the objects used, it is possible to obtain an increase in the food biomass production enriched with lipids or carbohydrates as appropriate to the biotechnological objectives.

This paper reports on a comprehensive study of the UV-shielding properties (namely, the sun protection factor and the factor of protection against UV-A radiation) and cytotoxicity (including photocytotoxicity) of amorphous and crystalline cerium(IV) phosphates. It has been shown that cerium(IV) phosphate NH4Ce2(PO4)3 is characterised by UV-shielding properties that are comparable to those of nanocrystalline TiO2 and CeO2. Moreover, cerium(IV) phosphates did not show toxicity towards cell cultures of NCTC L929 line mouse fibroblasts and human mesenchymal stem cells, in a wide range of concentrations, and even enhanced the proliferative activity of the latter. In a model study of the photoprotective properties of cerium(IV) phosphates on human mesenchymal stem cells, the pronounced protective effect of NH4Ce2(PO4)3 was observed, which was comparable to the shielding action of nanocrystalline CeO2. The results have shown that tetravalent cerium phosphates can be considered as promising UV-filters for sunscreen applications.

We studied the toxic effects of cerium and fluoride species on human dental pulp stem cells and epithelial cells of Cercopithecus aethiops as a surrogate for the human oral mucosa. The sequential use of CeCl3 and NH4F solutions in equimolar sub-toxic concentrations enabled the possible toxic effects of individual components to be avoided, ensuring the preservation of the metabolic activity of the cells due to the formation of CeF3 nanoparticles. Cerium fluoride nanoparticles and terbium-doped cerium fluoride nanoparticles exhibited neither cytotoxicity nor genotoxicity to dental pulp stem cells, even at high concentrations (10−4 M). In millimolar concentrations (from 10−5–10−6 M), these nanoparticles significantly increased the expression of genes responsible for the cell cycle, differentiation and proliferation. The formation of cerium fluoride on the surface of the mucous membrane and teeth provided protection against the development of carious lesions, periodontitis, ROS attacks and other inflammatory diseases of the oral cavity. Luminescent CeF3: Tb nanoparticles enabled the visualization of tooth enamel microcracks.

Nanoscale cerium dioxide (CeO2, nanoceria) possesses notable redox activity, which is actively used in advanced biomedical applications. The low toxicity, high biocompatibility and antioxidant activity of nanoceria make it a new generation nanozyme with a unique activity. Combination of nanoceria with various biologically active substances results in organic-inorganic nanocomposites possessing enhanced activity. Here, we synthesized a novel organic-inorganic hybrid material (Mil-CeO2) based on 2-(2-carboxylatoethyl)-1,1,1-trimethylhydrazinium and nanoceria, which has an ultra-small particle size, high antioxidant activity and pronounced biological activity. The analysis of cytotoxicity of the composite did not reveal any negative effects on the NCTC L929 mouse fibroblasts at concentrations below 10 mM. It was shown that the nanocomposite did not cause morphological changes in cells, or lead to cell death and mitochondrial membrane potential disruption, while maintaining viability in mouse fibroblasts in vitro. Additionally, we showed that Mil-CeO2 is capable of protecting cells from hydrogen peroxide (H2O2)-induced or radiation-induced oxidative stress.

The latest biomedical approaches based on the use of nanomaterials possessing luminescent properties make it possible to effectively visualize cancer cells or tissues, thus expanding diagnostic capabilities of the current bioimaging techniques. In this paper, a new scheme is proposed for the synthesis of cerium-containing carbon quantum dots (Ce-Qdots) of ultra-small size, promising for biomaging. Ce-Qdots have a high degree of biocompatibility, as well as remarkable redox activity. Cytotoxicity analysis performed using 4 human cell cultures confirmed the high degree of Ce-Qdots their biocompatibility. It was shown that Ce-Qdots in concentrations up to 200 mu g/ml do not have a negative effect on the metabolic, proliferative, migration and clonogenic activity of cell cultures after 24, 48 and 72 hours of co-incubation. Ce-Qdots can be considered as the basis of a new theranostic agent for bioimaging and targeted delivery of biologically active substances.

We studied cerium oxide-calcein nanoconjugate, which is capable of providing intracellular detection and simultaneous inactivation of reactive oxygen species (ROS).The synthesized nanoconjugate is easily uptaken by human mesenchymal stem cells (MSCs) and demonstrates antioxidant properties, protecting cells from H 2 O 2 -induced oxidative stress in vitro.Cerium oxide-calcein nanoconjugate neutralizes hydrogen peroxide, meanwhile releasing brightly fluorescent calcein from its surface, which is easily detected by fluorimeter or fluorescent microscope.This nanoconjugate is biocompatible and non-toxic to MSCs in concentrations below 2 mM.Such a theranostic agent can be considered as a promising tool for tracking the redox status of human MSCs in vivo.

A method is proposed for the preparation of stable sols of nanocrystalline cerium dioxide in nonpolar solvents, based on surface modification of CeO2 nanoparticles obtained by thermal hydrolysis of concentrated aqueous solutions of ammonium cerium(IV) nitrate with residues of 2-ethylhexanoic and octanoic acids. The synthesis was carried out at temperatures below 100 °C and did not require the use of expensive and toxic reagents. An assessment of the radical-scavenging properties of the obtained sols using the superoxide anion-radical neutralization model revealed that they demonstrate notable antioxidant activity. The results obtained indicate the potential of the nanoscale cerium dioxide sols in nonpolar solvents to be used for creating nanobiomaterials possessing antioxidant properties.

The development of advanced composite biomaterials combining the versatility and biodegradability of polymers and the unique characteristics of metal oxide nanoparticles unveils new horizons in emerging biomedical applications, including tissue regeneration, drug delivery and gene therapy, theranostics and medical imaging. Nanocrystalline cerium(IV) oxide, or nanoceria, stands out from a crowd of other metal oxides as being a truly unique material, showing great potential in biomedicine due to its low systemic toxicity and numerous beneficial effects on living systems. The combination of nanoceria with new generations of biomedical polymers, such as PolyHEMA (poly(2-hydroxyethyl methacrylate)-based hydrogels, electrospun nanofibrous polycaprolactone or natural-based chitosan or cellulose, helps to expand the prospective area of applications by facilitating their bioavailability and averting potential negative effects. This review describes recent advances in biomedical polymeric material practices, highlights up-to-the-minute cerium oxide nanoparticle applications, as well as polymer-nanoceria composites, and aims to address the question: how can nanoceria enhance the biomedical potential of modern polymeric materials?

In spite of good sun protection characteristics, nanocrystalline TiO2 and ZnO widely used as inorganic UV filters can display a negative effect on skin. Nanocrystalline cerium dioxide was proposed as a promising component of sun protection cosmetics, however, no quantitative comparison of sun protection characteristics of CeO2 with other metal oxides was carried out until now. In this work, we experimentally determined for the first time the values of sun protection factor and UVA protection factor for CeO2 nanoparticles in accordance with the State Standard ISO 24443-2016 and compared them with characteristics of TiO2 and ZnO. Effect of size factor on CeO2 sun protection characteristics has been found.

In spite of the wide application of nanodisperse tungsten oxide (from photo- and electrochromic devices to biomedical materials), its physicochemical properties were studied insufficiently. In this work, we have performed a comparative analysis of photochromic and photocatalytic properties of polyvinylpyrrolidone-stabilized tungsten oxide nanoparticles prepared by ion exchange and precipitation from sodium tungstate solution. Reversible UV-induced reduction of Methylene Blue dye in the presence of photochromic tungsten oxide sol has been shown, the dependence of photochromic properties of tungsten oxide sols on sodium cation concentration in solution has been revealed.

A water- and alcohol-soluble cerium oxide-curcumin conjugate was obtained by co-evaporation with poly(N-vinylpyrrolidone) (PVP). A nanocomposite consisting of hybrid organic-inorganic particles was stable in a wide range of pH values. Its properties were evaluated using nine cell lines: normal (MDBK, ST, Vero) and malignant (L929, T98G, HEp-2, A549, RIN-m5F, Hep G2). PVP-stabilised nanoceria was shown to inhibit autoxidation of curcumin, to enhance curcumin photostability, to promote bioaccumulation and to affect curcumin cytotoxicity and photocytotoxicity, depending on cell type, being more toxic to cancer cells in a selective manner. Under the conditions of UVA/UVC or H2O2-induced oxidative stress, the nanoceria-PVP-curcumin (NPC) conjugate was found to possess a selective cytotoxicity: it caused drastic inhibition of metabolic activity or a decrease in the total number of tumour cells, while in non-transformed cultures under the same conditions, the nanoceria-PVP-curcumin conjugate protected cells from these damaging factors. The NPC-conjugate, unlike curcumin itself, demonstrated a photosensitising effect in tumour cell cultures, while protecting non-transformed cultures from the damaging effects of UV radiation or oxidative stress. Based on the results obtained, we strongly believe that this novel hybrid material has enhanced characteristics compared to other curcumin formulations, and can be considered as a potent drug for biomedical applications, including cancer therapy.

Cerium oxide nanoparticles (nanoceria) possess enormous biological activity, wherein many aspects related to the biological properties of nanoceria still remain unclear. In the present chapter, we have tried to explore the possible biological mechanisms of nanoceria action in terms of the catalytic activity of CeO2 particles and chemical behavior of cerium ions. Based on the analysis of a large number of about 500 primary sources, we can draw a conclusion that the ability to inactivate reactive oxygen species (oxophilicity) and to scavenge free radicals, as well as the phosphatase-like activity, is typical for both ceria and cerium ions. In turn, ceria nanoparticles specifically interact with electromagnetic radiation, but cannot participate in the natural enzymatic cycles of plants and animals. Future promising therapeutic applications of cerium oxide include delivery of various drugs and treatment of the diseases associated with oxidative stress, redox therapy of oncological diseases, adjuvant in antiviral therapy, prebiotic and immunomodulator, carrier and restriction enzyme mimetic in gene therapy, modulator of signal transduction in neurology, etc.

Tungsten oxide-based bulk and nanocrystalline materials are widely used as photocatalytic and photo- and electrochromic materials, as well as materials for biomedical applications. In our work, we focused our attention on the effect of sodium cations on the structure and photochromic properties of the WO3@PVP aqueous sols. To establish the effect, the sols were synthesized by either simple pH adjusting of sodium or ammonium tungstates' solutions, or using an ion exchange technique to remove the cations from the materials to the greatest possible extent. We showed that the presence of sodium cations in WO3@PVP favors the formation of reduced tungsten species (W+5) upon UV irradiation of the materials, strongly affecting their photochromic and photocatalytic properties. The pronounced photoreductive properties of WO3@PVP sols in photocatalytic reactions were demonstrated. Due to photoreductive properties, photochromic sols of tungsten oxide can act as effective photoprotectors in photooxidation processes. We believe that our work provides a considerable contribution to the elucidation of photochromic and redox phenomena in WO3-based materials.