Biomaterials Based on Carbon Nanotube Nanocomposites of Poly(styrene-b-isobutylene-b-styrene): The Effect of Nanotube Content on the Mechanical Properties, Biocompatibility and Hemocompatibility.

Nanocomposites based on poly(styrene-block-isobutylene-block-styrene) (SIBS) and single-walled carbon nanotubes (CNTs) were prepared and characterized in terms of tensile strength as well as bio- and hemocompatibility. It was shown that modification of CNTs using dodecylamine (DDA), featured by a long non-polar alkane chain, provided much better dispersion of nanotubes in SIBS as compared to unmodified CNTs. As a result of such modification, the tensile strength of the nanocomposite based on SIBS with low molecular weight (Mn = 40,000 g mol-1) containing 4% of functionalized CNTs was increased up to 5.51 ± 0.50 MPa in comparison with composites with unmodified CNTs (3.81 ± 0.11 MPa). However, the addition of CNTs had no significant effect on SIBS with high molecular weight (Mn~70,000 g mol-1) with ultimate tensile stress of pure polymer of 11.62 MPa and 14.45 MPa in case of its modification with 1 wt% of CNT-DDA. Enhanced biocompatibility of nanocomposites as compared to neat SIBS has been demonstrated in experiment with EA.hy 926 cells. However, the platelet aggregation observed at high CNT concentrations can cause thrombosis. Therefore, SIBS with higher molecular weight (Mn~70,000 g mol-1) reinforced by 1-2 wt% of CNTs is the most promising material for the development of cardiovascular implants such as heart valve prostheses.

Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Study of Nanostructured TiO2 Rutile with Hierarchical 3D-Architecture. Effect of the Synthesis and Calcinations Temperature.

The effect of TiCl4 hydrolysis temperature on the structural, textural and morphological properties of the resulting rutile and on the changes of these properties upon calcination was studied. The XRD, Raman spectroscopy, mercury porosimetry, BET, SEM and TEM studies have revealed that TiO2 rutile has a hierarchical 3D-architecture. The obtained nanostructured rutile had a cauliflowerlike/ spherical morphology composed of fan-shaped nanofibers. Rutile samples were shown to have a heterogeneous pore structure including micro-, meso- and macropores with a BET surface area of 110-140 m2/g. According to the mercury porosimetry, among mesopores and macropores the latter dominate in the samples. Elevation of the synthesis temperature from 50-70 to 80-90 °C decreased the fraction of macropores from 95 to 70%. The BET method showed that the samples synthesized at low temperatures (50-70 °C) contain 30-44% of micropores in the total amount of mesopores and micropores. The fraction of micropores decreases to 25-18% with a subsequent increase in the fraction of mesopores as the synthesis temperature is raised to 80-90 °C. As shown by a study of the samples upon calcination in the temperature range of 100-1000 °C, temperature is the key factor that produces changes in the crystallites size, nanofiber length and packing density, and 3D particle shape at different levels of the hierarchical system and determines features of the porous structure and morphological properties of nanostructured rutile. The assessment of photocatalytic activity in the oxidation of acetone vapor demonstrated that, regardless of the hydrolysis temperature, the synthesized samples of nanostructured rutile are able to oxidize acetone vapor to carbon dioxide and water. In the process, activity of the samples is comparable with that of commercial photocatalysts under UV light and is superior to the activity of commercial photocatalysts P25 (2-4 times) and TiO2 KRONOS vlp 7000 (1.2-2 times) under visible light in dependence on the synthesis temperature.

Non-agglomerated silicon-organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties.

The development of efficient and convenient systems for the delivery of nucleic-acid-based drugs into cells is an urgent task. А promising approach is the use of various nanoparticles. Silica nanoparticles can be used as vehicles to deliver nucleic acid fragments into cells. In this work, we developed a method for the synthesis of silicon-organic (Si-NH2) non-agglomerated nanoparticles by the hydrolysis of aminopropyltriethoxysilane (APTES). The resulting product forms a clear solution containing nanoparticles in the form of low molecular weight polymer chains with [─Si(OH)(C3H6NH2)O─] monomer units. Oligonucleotides (ODN) were conjugated to the prepared Si-NH2 nanoparticles using the electrostatic interaction between positively charged amino groups of nanoparticles and negatively charged internucleotide phosphate groups in oligonucleotides. The Si-NH2 nanoparticles and Si-NH2·ODN nanocomplexes were characterized by transmission electron microscopy, atomic force microscopy and IR and electron spectroscopy. The size and zeta potential values of the prepared nanoparticles and nanocomplexes were evaluated. Oligonucleotides in Si-NH2·ODN complexes retain their ability to form complementary duplexes. The Si-NH2 Flu nanoparticles and Si-NH2·ODNFlu nanocomplexes were shown by fluorescence microscopy to penetrate into human cells. The Si-NH2 Flu nanoparticles predominantly accumulated in the cytoplasm whereas ODNFlu complexes were predominantly detected in the cellular nuclei. The Si-NH2·ODN nanocomplexes demonstrated a high antisense activity against the influenza A virus in a cell culture at a concentration that was lower than their 50% toxic concentration by three orders of magnitude.

One-step chemical vapor deposition synthesis and supercapacitor performance of nitrogen-doped porous carbon-carbon nanotube hybrids.

Novel nitrogen-doped carbon hybrid materials consisting of multiwalled nanotubes and porous graphitic layers have been produced by chemical vapor deposition over magnesium-oxide-supported metal catalysts. CN x nanotubes were grown on Co/Mo, Ni/Mo, or Fe/Mo alloy nanoparticles, and MgO grains served as a template for the porous carbon. The simultaneous formation of morphologically different carbon structures was due to the slow activation of catalysts for the nanotube growth in a carbon-containing gas environment. An analysis of the obtained products by means of transmission electron microscopy, thermogravimetry and X-ray photoelectron spectroscopy methods revealed that the catalyst's composition influences the nanotube/porous carbon ratio and concentration of incorporated nitrogen. The hybrid materials were tested as electrodes in a 1M H2SO4 electrolyte and the best performance was found for a nitrogen-enriched material produced using the Fe/Mo catalyst. From the electrochemical impedance spectroscopy data, it was concluded that the nitrogen doping reduces the resistance at the carbon surface/electrolyte interface and the nanotubes permeating the porous carbon provide fast charge transport in the cell.

Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions.

Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide.

Influenza is a heavy socially significant viral infection that affects humans, birds, and wild and domestic animals. The threat of existing and new highly pathogenic subtypes of influenza A virus (IAV) makes it necessary to develop an effective drug that may affect different IAV strains. For this purpose, oligodeoxynucleotides (DNA fragments) attached to titanium dioxide (TiO2) nanoparticles through a polylysine linker, forming TiO2·PL-DNA nanocomposites, that penetrated into cells without transfection agents were used. For the first time, efficient (≥99.9%) suppression of the reproduction of different subtypes of IAV, including highly pathogenic H5N1 and H1N1, was achieved. These results were obtained using the TiO2·PL-DNA nanocomposite bearing a single antisense oligodeoxynucleotide (0.1µM) targeted to the conserved 3'-noncoding region of RNA segment 5, which is common to all tested strains. Very efficient suppression of the reproduction of different subtypes of IAV was probably achieved due to the use of the proposed delivery system for oligonucleotides in the form of the TiO2·PL-DNA nanocomposites. These results indicate the possibility of creating an efficient drug to affect existing and newly emerging pathogenic IAV strains.

High-performance method for specific effect on nucleic acids in cells using TiO2~DNA nanocomposites.

Nanoparticles are used to solve the current drug delivery problem. We present a high-performance method for efficient and selective action on nucleic acid target in cells using unique TiO(2)·PL-DNA nanocomposites (polylysine-containing DNA fragments noncovalently immobilized onto TiO(2) nanoparticles capable of transferring DNA). These nanocomposites were used for inhibition of human influenza A (H3N2) virus replication in infected MDCK cells. They showed a low toxicity (TC(50) ≈ 1800 µg/ml) and a high antiviral activity (>99.9% inhibition of the virus replication). The specificity factor (antisense effect) appeared to depend on the delivery system of DNA fragments. This factor for nanocomposites is ten-times higher than for DNA in the presence of lipofectamine. IC(50) for nanocomposites was estimated to be 1.5 µg/ml (30 nM for DNA), so its selectivity index was calculated as ~1200. Thus, the proposed nanocomposites are prospective for therapeutic application.