Biocompatible dextran-coated gadolinium-doped cerium oxide nanoparticles as MRI contrast agents with high T1 relaxivity and selective cytotoxicity to cancer cells.

Gd-based complexes are widely used as magnetic resonance imaging (MRI) contrast agents. The safety of previously approved contrast agents is questionable and is being re-assessed. The main causes of concern are possible gadolinium deposition in the brain and the development of systemic nephrogenic fibrosis after repeated use of MRI contrasts. Thus, there is an urgent need to develop a new generation of MRI contrasts that are safe and that have high selectivity in tissue accumulation with improved local contrast. Here, we report on a new type of theranostic MRI contrast, namely dextran stabilised, gadolinium doped cerium dioxide nanoparticles. These ultra-small (4-6 nm) Ce0.9Gd0.1O1.95 nanoparticles have been shown to possess excellent colloidal stability and high r1-relaxivity (3.6 mM-1 s-1). They are effectively internalised by human normal and cancer cells and demonstrate dose-dependent selective cytotoxicity to cancer cells.

The first amorphous and crystalline yttrium lactate: synthesis and structural features.

The synthesis and crystal structure of the first molecular yttrium lactate complex, Y(Lac)3(H2O)2, is reported, where the coordination sphere of yttrium is saturated with lactate ligands and water molecules, resulting in a neutral moiety. In Y(Lac)3(H2O)2, hydrogen bonding between α-hydroxy groups and water molecules allows for the formation of 2D layers. A subtle variation in synthetic conditions, i.e. a slight increase in pH (5.5 instead of 4.5) promoted the formation of a semi-amorphous fibrous material with a presumed chemical composition of Y4(OH)5(C3H5O3)7·6H2O. The flattened fibres in this material are responsible for its good flexibility and foldability.

Nanoceria-curcumin conjugate: Synthesis and selective cytotoxicity against cancer cells under oxidative stress conditions.

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.

Photo-induced toxicity of tungsten oxide photochromic nanoparticles.

We synthesised a new type of photochromic tungsten oxide nanoparticles, analysed their photocatalytic activity and carried out a thorough analysis of their effect on prokaryotic and eukaryotic organisms. Ultrasmall hydrated tungsten oxide nanoparticles were prepared by means of hydrothermal treatment of tungstic acid in the presence of polyvinylpyrrolidone as a template, stabiliser and growth regulator. Tungstic acid was synthesised through an ion-exchange method using sodium tungstate solution and a strongly acidic cation exchange resin. Upon illumination, photochromic nanoparticles of WO3 were shown to increase greatly their toxicity against both bacterial (both gram-positive and gram-negative - P. aeruginosa, E. coli and S. aureus) and mammalian cells (primary mouse embryonic fibroblasts); under the same conditions, fungi (C. albicans) were less sensitive to the action of tungsten oxide nanoparticles. UV irradiation of primary mouse fibroblasts in the presence of WO3 nanoparticles demonstrated a time- and dose-dependent toxic effect, the latter leading to a significant decrease in dehydrogenase activity and an increase in the number of dead cells. WO3 nanoparticles were photocatalytically active under both UV light and even diffused daylight filtered through a window glass, leading to indigo carmine organic dye discolouration. The obtained experimental data not only show good prospects for biomedical applications of tungsten trioxide, but also demonstrate the need for clear control of biosafety when it is used in various household materials and appliances.

Unexpected Effects of Activator Molecules' Polarity on the Electroreological Activity of Titanium Dioxide Nanopowders.

Titanium dioxide nanoparticles, obtained using the sol-gel method and modified with organic solvents, such as acetone, acetonitrile, benzene, diethyl ether, dimethyl sulfoxide, toluene, and chloroform, were used as the filler of polydimethylsiloxane-based electrorheological fluids. The effect of electric field strength on the shear stress and yield stress of electrorheological fluids was investigated, as well as the spectra of their dielectric relaxation in the frequency range from 25 to 106 Hz. Modification of titanium dioxide by polar molecules was found to enhance the electrorheological effect, as compared with unmodified TiO2, in accordance with the widely accepted concept of polar molecule dominated electrorheological effect (PM-ER). The most unexpected result of this study was an increase in the electrorheological effect during the application of nonpolar solvents with zero or near-zero dipole moments as the modifiers. It is suggested that nonpolar solvents, besides providing additional polarization effects at the filler particles interface, alter the internal pressure in the gaps between the particles. As a result, the filler particles are attracted to one another, leading to an increase in their aggregation and the formation of a network of bonds between the particles through liquid bridge contacts. Such changes in the electrorheological fluid structure result in a significant increase in the mechanical strength of the structures that arise when an electric field is applied, and an increase in the observed electrorheological effect in comparison with the unmodified titanium dioxide.

Experimental Study of the Effects of Nanodispersed Ceria on Wound Repair.

We studied the effects of nanodispersed ceria on wound healing in vitro and in vivo. It was found that cerium dioxide stimulated wound healing, which manifested in shrinkage of burn wound area (by 1.5 times) and intensification (by 2.4 times) marginal epithelialization.

Panthenol-stabilized cerium dioxide nanoparticles for cosmeceutic formulations against ROS-induced and UV-induced damage.

A method of panthenol-stabilized cerium dioxide nanoparticles synthesis was developed and their effect on the survival rate of human epidermoid cancer cells HEp-2 and diploid epithelial swine testicular cell line (ST-cells) under oxidative stress conditions induced by hydrogen peroxide introduction and UV irradiation was studied. The results obtained indicate that the use of panthenol as a stabilizer supposedly provides a substantial increase in the efficiency of protection. The degree of protection is determined by panthenol-to-ceria molar ratio. The combination of panthenol and nano-ceria protects biological objects under study from reactive oxygen species (ROS) and UV-irradiation more effectively than individual panthenol or ceria. The protective action of panthenol-stabilized cerium dioxide nanoparticles depends strongly on their composition and the means of their application.

[Nanocrystaline ceria based materials--perspectives for biomedical application].

Nanocrystalline ceria possesses a unique complex of physical and chemical properties making it highly bioactive material. In this review, modern data on the action of nanocrystalline ceria on cells, micro- and macroorganisms are analyzed. Special attention is paid to the analysis of the factors affecting protective properties of CeO2 with respect to the living systems.

[New algorithm for calculation of N-H peptide bond order parameter by the method of molecular dynamic modeling].

A new algorithm was proposed for calculation of N-H bond order parameter from molecular dynamics (MD) trajectories. The MD simulation of the HIV-1 protease (3.4.23.16) with monoprotonated active centre was performed for the algorithm verification. It has been shown that the protease in aqueous solution at pH 3.5-6.5 adopts a set of conformations, which are intermediate between the "open" and "closed" ones. The N-H bond order parameters calculated from the MD trajectory are in agreement with experimental NMR data.

The improvement of the algorithm for order parameter calculation (S2) from molecular dynamics simulation using the correlation motion function.

The generalized order parameter, S2, calculated from MD simulation trajectory using time-dependent internal Correlation Motion Function (CMF) agrees well with NMR derived S2 processed with the extended model-free analysis approach. However, the former lies considerably lower comparing to simple model-free derived data from NMR experiments. In the present study we analyze possible reasons of such disagreement. In the general case we propose to use preexponential factors from expression for internal CMF rather than ordinary S2 values. Particularly, in case of the simple model-free S(2) experimental values we suggest comparing them with S2(eff)=1+S2-Sf2 computed from MD simulation data. We show that the S2(eff) values are in a good agreement with NMR derived S2 values obtained using the simple model-free analysis.

[Generalized ordering parameter S2 for N-H peptide bonding as measure of the conformational flexibility of proteins: comparison of algorithms of S2 calculation from molecular dynamics simulation data]. / Obobshchennyi parametr uporiadocheniia S2 dlia sviazi N-H peptidnoi gruppy kak mera konformatsionnoi podvizhnosti belka: sravnenie algoritmov rascheta S2 iz dannykh simuliatsii molekuliarnoi dinamiki.

NMR spectroscopy in combination with molecular dynamics (MD) simulation technique is a powerful tool for investigation of biomolecule conformations. In the present study we compare the two algorithms of calculation of the generalized order parameter S2 for the peptide N-H bond from MD simulation data. The program based on this algorithm has been written and the effect of an adjustible parameter on results of calculation was studied. HIV-1 protease MD simulation was performed during 7.36 ns using GROMACS 3.1.4. software package. The calculated order parameter values are in good agreement with those obtained by other authors using NMR.