Macrophages as carriers of boron carbide nanoparticles dedicated to boron neutron capture therapy.

BACKGROUND: The use of cells as carriers for the delivery of nanoparticles is a promising approach in anticancer therapy, mainly due to their natural properties, such as biocompatibility and non-immunogenicity. Cellular carriers prevent the rapid degradation of nanoparticles, improve their distribution, reduce cytotoxicity and ensure selective delivery to the tumor microenvironment. Therefore, we propose the use of phagocytic cells as boron carbide nanoparticle carriers for boron delivery to the tumor microenvironment in boron neutron capture therapy. RESULTS: Macrophages originating from cell lines and bone marrow showed a greater ability to interact with boron carbide (B4C) than dendritic cells, especially the preparation containing larger nanoparticles (B4C 2). Consequently, B4C 2 caused greater toxicity and induced the secretion of pro-inflammatory cytokines by these cells. However, migration assays demonstrated that macrophages loaded with B4C 1 migrated more efficiently than with B4C 2. Therefore, smaller nanoparticles (B4C 1) with lower toxicity but similar ability to activate macrophages proved to be more attractive. CONCLUSIONS: Macrophages could be promising cellular carriers for boron carbide nanoparticle delivery, especially B4C 1 to the tumor microenvironment and thus prospective use in boron neutron capture therapy.

Synthesis and Characterization of Boron Carbide Nanoparticles as Potential Boron-Rich Therapeutic Carriers.

Boron carbide is one of the hardest materials in the world which can be synthesized by various methods. The most common one is a carbothermic or magnesiothermic reduction of B2O3 performed at high temperatures, where the obtained powder still requires grinding and purification. The goal of this research is to present the possibility of synthesizing B4C nanoparticles from elements via vapor deposition and modifying the morphology of the obtained powders, particularly those synthesized at high temperatures. B4C nanoparticles were synthesized in the process of direct synthesis from boron and carbon powders heated at the temperature of 1650 °C for 2 h under argon and characterized by using scanning electron microscopy, transmission electron microscopy, atomic force microscopy, X-ray diffraction analysis, and dynamic light scattering measurements. The physicochemical characteristics of B4C nanoparticles were determined, including the diffusion coefficients, hydrodynamic diameter, electrophoretic mobilities, and zeta potentials. An evaluation of the obtained B4C nanoparticles was performed on several human and mouse cell lines, showing the relation between the cytotoxicity effect and the size of the synthesized nanoparticles. Assessing the suitability of the synthesized B4C for further modifications in terms of its applicability in boron neutron capture therapy was the overarching goal of this research.

Ceramic Matrix Composites Obtained by the Reactive Sintering of Boron Carbide with Intermetallic Compounds from the Ti-Si System.

In this study, we investigated the effect of adding two different intermetallics, Ti5Si3 and TiSi2, for the preparation of TiB2-SiC-B4C composites. As part of the research, stoichiometric composites consisting only of two phases TiB2 and SiC were obtained. The TiB2-SiC-B4C composites were prepared via pressureless sintering. The presence of the phases in the sintered composites was confirmed using X-ray diffraction and scanning electron microscopy. The SEM-EDS examination revealed that the TiB2 and SiC phases were formed during the composite process synthesis and were distributed homogeneously in the B4C matrix. The obtained results allowed us to usually exceed 2000 °C and the use of specialized equipment for firing, that is, vacuum or protective atmosphere furnaces as well as control and measurement equipment. Such an approach generates high costs that are decisive for the economics of the technological processes. In the case of our compositions, it is possible to lower the temperature to 1650 °C. The TiB2-SiC-B4C composites were classified as UHTCs.

Fly Ash from Lignite Combustion as a Filler for Rubber Mixes-Part II: Chemical Valorisation of Fly Ash.

Fly ash (FA) fractions with a particle size of 63 µm < FA < 250 µm obtained by sieve fractionation were used as a partial carbon black (CB) replacement in a rubber mixture based on styrene-butadiene rubber (SBR). In order to improve the interactions at the interface between rubber and fractionated ash, at the stage of preparing the rubber mixtures, two different vinyl silanes were added to the system: Vinyltrimethoxysilane (U-611) or Vinyl-tris (2-methoxy-ethoxy) silane (LUVOMAXX VTMOEO DL50), silane with epoxy groups: 3-(glycidoxypropyl)trimethoxysilane (U-50) or sulfur functionalized silanes: containing sulfide bridges: Bis(triethoxysilylpropyl)polysulfide silane (Si-266) or mercapto groups: Mercaptopropyltrimethoxysilane (Dynaslan MTMO). The conducted research confirmed the effectiveness of silanization with selected functional silanes, from the point of view of improving the processing and operational properties of vulcanizates, in which CB is partially replaced with the finest fractions of fly ash. The silanization generally increased the interaction at the rubber−ash interface, while improving the degree of filler dispersion in the rubber mixture. The results of TGA and FTIR analyses confirmed the presence of silanes chemically bonded to the surface of fly ash particles. SEM tests and determination of the bound rubber (BdR) content show that the introduction of the silanes to the mixture increases the degree of ash dispersion (DI) and the Payne effect, which is the greatest when mercaptosilane was used for modification. The highest increase in torque, which was recorded in the case of rubber mixtures containing sulfur silanes and silane with epoxy groups, may be due to their participation in the vulcanization process, which is confirmed by the results of vulcametric studies. The lowest values of mechanical strength, elongation at break, and the highest hardness of vulcanizates obtained in this case may be the result of the over-crosslinking of the rubber. The addition of sulfur-containing silanes significantly slowed down the vulcanization process, which is particularly visible (up to three times extension of the t90 parameter, compared to mixtures without silane) in the case of Si-266. The addition of silanes, except for Si-266 (with a polysulfide fragment), generally improved the abrasion resistance of vulcanizates. The Dynaslan MTMO silane (with mercapto groups) performs best in this respect. Proper selection of silane for the finest fraction of fly ash in the rubber mixtures tested allows for an increase in the mechanical strength of their vulcanizates from 9.1 to 17 MPa, elongation at break from 290 to 500%, hardness from 68 to 74 °ShA, and reduction in abrasion from 171 to 147 mm3.

Fly Ash from Lignite Combustion as a Filler for Rubber Mixes. Part I: Physical Valorization of Fly Ash.

The potential use of fly ash (FA) originating from lignite combustion at the Belchatow Power Plant (Poland) as filler for rubber mixes was evaluated. Samples of fly ash collected from heaps created in different years were compared according to their chemical and phase composition, particle size distribution, and morphology. The sieve fractionation of fly ash results in size fractions of different chemical structures, phase compositions, and morphologies, reflected in changes to their specific surface area, surface energy, and activity in rubber mixes. Fractionation turned out to be more effective than grinding from the point of view of using ash as a filler for rubber mixes, because it results in higher specific surface area (SSA) and chemical composition differentiation. Carbon black can be replaced by up to 40% by weight with the fly ash fraction (FFA) of dimensions below 125 µm, without any significant deterioration in the mechanical properties of styrene butadiene rubber (SBR) vulcanizates filled with 50 phr of active carbon black (N 220). Despite the larger fly ash fraction of grain dimensions in the range between 125 and 250 µm presenting the highest specific surface area, the particle size adversely affects its strengthening effect in rubber. Taking into account all the tests performed, ranging from morphology, Payne effect and bound rubber, to mechanical and abrasion tests, the highest potential effectivity is presented by a sample containing 30 phr of N 220 and 20 phr of FFA of grain sizes from 63 to 125 µm. The obtained results indicate that fractionation seems to be an effective physical method of fly ash valorization.

Synthesis and Photoluminescence Properties of Pr3+-Doped Ba0.5Ca0.5TixZr(1-x)O3 Perovskite Diphasic Ceramics Obtained by the Modified Pechini Method.

The Pr3+-doped solid solutions from (Ba,Ca)(Ti,Zr)O3 (BCTZO) system were successfully synthesized using an efficient and low-energy consuming route-the Pechini method combined with the sintering at relatively low temperature (1450 °C). The obtained materials were characterized by means of X-ray diffraction (XRD) and scanning electron microscopy (SEM). The dielectric properties were systematically studied. The Pr3+-doped BCTZO diphasic material generates intense and broad red photoluminescence (PL) emission at room temperature. The optical properties were significantly improved with the Ti4+ substitution by Zr4+ ions. As a result, the Pr3+-doped (Ba,Ca)(Ti,Zr)O3 ceramics is a promising candidate for environmentally friendly, multifunctional material by combining good dielectric and photoluminescent properties with prognosis for the manifestation of strong photoluminescent and mechanoluminescent effects.

Alumina-Toughened-Zirconia with Low Wear Rate in Ball-on-Flat Tribological Tests at Temperatures to 500 °C.

An alumina-toughened zirconia (ATZ) material, fabricated using a procedure consisting of the common sintering of two different zirconia powders, was tested using the ball-on-disc method in a temperature range between room temperature and 500 °C. Corundum balls were used as a counterpart. The ATZ composite behaviour during tests was compared with that of commonly used α-alumina and tetragonal zirconia sintered samples. At temperatures over 350 °C, a drastic decrease in the wear rate of the material was detected. SEM analyses proved that, in such conditions, nearly the whole surface of the sliding material was covered with a layer of deformed submicrometric grains, which limited contact with the part of material that was not deformed. The mentioned layer was relatively strongly connected with the material, increased its resistance, and decreased its coefficient of friction. As a reference, commonly used materials, namely commercial alumina and tetragonal zirconia, were tested. The wear parameters of the composite were significantly better than those registered for the materials prepared of commercial powders.

Phenomena Occurring upon the Sintering of a Mixture of Yttria-Zirconia Nanometric Powder and Sub-Micrometric Pure Zirconia Powder.

Mixtures of powders essentially differing in their particle morphology and size were applied to prepare polycrystals in a Y2O3-ZrO2 system. An yttria-zirconia solid solution nanometric powder with a Y2O3 concentration of 3.5% was prepared by subjecting co-precipitated gels to hydrothermal treatment at 240 °C. The crystallization occurred in distilled water. The pure zirconia powders composed of elongated and sub-micrometer size particles were also manufactured through the hydrothermal treatment of pure zirconia gel, although in this case, the process took place in the NaOH solution. Mixtures of the two kinds of powder were prepared so as to produce a mean composition corresponding to an yttria concentration of 3 mol%. Compacts of this powder mixture were sintered, and changes in phase composition vs. temperature were studied using X-ray diffraction. The dilatometry measurements revealed the behavior of the powder compact during sintering. The polished surfaces revealed the microstructure of the resulting polycrystal. Additionally, the electron back scattering diffraction technique (EBSD) allowed us to identify symmetry between the observed grains. Hardness, fracture toughness, and mechanical strength measurements were also performed.

Hydrothermal Aging of ATZ Composites Based on Zirconia Made of Powders with Different Yttria Content.

The presented work concerns the development and investigation of three different grades of ZrO2 materials containing Al2O3 particles (ATZ-Alumina Toughened Zirconia ceramics with 2.3-20 vol.% of alumina). The zirconia powders containing 3 mol.% of yttria were synthesized by a precipitation/calcination method and fabricated from two different zirconia powders with different yttria content. Then, the selected ATZ composites (ATZ-B, ATZ-10 and ATZ-20) were prepared by means of conventional mixing, compacting and sintering at 1450 °C for 1.5 h. The phase composition, microstructure, relative density and basic mechanical properties were determined. Uniform microstructures with relative densities over 99% of theoretical density, hardness values between 12.0-13.8 GPa, flexural strength up to 1 GPa and outstanding fracture toughness of 12.7 MPa⋅m1/2 were obtained. The aging susceptibility of alumina toughened zirconia materials, as a consequence of hydrothermal treatment, was investigated. The aim of this study was to determine the influence of LTD (low temperature degradation) on the tetragonal to monoclinic phase transitions and on the flexural strength of hydrothermally aged specimens. The results were compared to those obtained for commercially available tetragonal zirconia-based materials containing 3 mol.% of yttria. This research shows that ATZ composites that have excellent mechanical properties and sufficient hydrothermal aging resistance can be attained and later used in technical and biomedical applications.

The Preparation of Dense Materials in the MgO-ZrO2 System by the Application of Nanometric Powders.

Crystallization under hydrothermal conditions allowed us to prepare nanometric powders in the MgO-ZrO2 system of different magnesia concentrations. Sintering runs of these powder compacts studied using dilatometry measurements during heating and cooling revealed essential differences in their behavior. The microstructure of the resulting polycrystal is strongly related to the magnesia content in the starting powder, which strongly influences the phase composition of the resulting material and its mechanical properties. It should be emphasized that the novel processing method of such materials differs from the usual applied technology and leads to magnesia-zirconia materials of a different microstructure than that of "classical" materials of this kind.

Combustion Synthesis of Aluminum Oxynitride in Loose Powder Beds.

This paper describes combusting loose powder beds of mixtures of aluminum metal powders and aluminum oxide powders with various grain sizes under various nitrogen pressure. The synthesis conditions required at least 20/80 weight ratio of aluminum metal powder to alumina powder in the mix to reach approximately 80 wt% of γ-AlON in the products. Finely ground fused white alumina with a mean grain size of 5 µm was sufficient to achieve results similar to very fine alumina with 0.3 µm grains. A lower nitrogen pressure of 1 MPa provided good results, allowing a less robust apparatus to be used. The salt-assisted combustion synthesis upon addition of 10 wt% of ammonium nitrite resulted in a slight increase in product yield and allowed lower aluminum metal powder content in mixes to be ignited. Increasing the charge mass five times resulted in a very similar γ-AlON yield, providing a promising technology for scaling up. Synthesis in loose powder beds could be utilized for effective production of relatively cheap and uniform AlON powder, which could be easily prepared for forming and sintering without intensive grounding and milling, which usually introduce serious contamination.

The Mechanism of Adsorption of Rh(III) Bromide Complex Ions on Activated Carbon.

In the paper, the mechanism of the process of the Rh(III) ions adsorption on activated carbon ORGANOSORB 10-AA was investigated. It was shown, that the process is reversible, i.e., stripping of Rh(III) ions from activated carbon to the solution is also possible. This opens the possibility of industrial recovery of Rh (III) ions from highly dilute aqueous solutions. The activation energies for the forward and backward reaction were determined These are equal to c.a. 7 and 0 kJ/mol. respectively. Unfortunately, the efficiency of this process was low. Obtained maximum load of Rh(III) was equal to 1.13 mg per 1 g of activated carbon.

Surface Properties and Morphology of Boron Carbide Nanopowders Obtained by Lyophilization of Saccharide Precursors.

The powders of boron carbide are usually synthesized by the carbothermal reduction of boron oxide. As an alternative to high-temperature reactions, the development of the carbothermal reduction of organic precursors to produce B4C is receiving considerable interest. The aim of this work was to compare two methods of preparing different saccharide precursors mixed with boric acid with a molar ratio of boron to carbon of 1:9 for the synthesis of B4C. In the first method, aqueous solutions of saccharides and boric acid were dried overnight at 90 °C and pyrolyzed at 850 °C for 1 h under argon flow. In the second method, aqueous solutions of different saccharides and boric acid were freeze-dried and prepared in the same way as in the first method. Precursors from both methods were heat-treated at temperatures of 1300 to 1700 °C. The amount of boron carbide in the powders depends on the saccharides, the temperature of synthesis, and the method of precursor preparation.

Boron-Rich Boron Carbide Nanoparticles as a Carrier in Boron Neutron Capture Therapy: Their Influence on Tumor and Immune Phagocytic Cells.

The aim of the work was to study the interaction between boron-rich boron carbide nanoparticles and selected tumor and immune phagocytic cells. Experiments were performed to investigate the feasibility of the application of boron carbide nanoparticles as a boron carrier in boron neutron capture therapy. Boron carbide powder was prepared by the direct reaction between boron and soot using the transport of reagents through the gas phase. The powder was ground, and a population of nanoparticles with an average particle size about 80 nm was selected by centrifugation. The aqueous suspension of the nanoparticles was functionalized with human immunoglobulins or FITC-labeled human immunoglobulins and was then added to the MC38 murine colon carcinoma and to the RAW 264.7 cell line of mouse macrophages. Flow cytometry analysis was used to determine interactions between the functionalized boron carbide nanoparticles and respective cells. It was shown that B4C-IgG nanoconjugates may bind to phagocytic cells to be internalized by them, at least partially, whereas such nanoconjugates can only slightly interact with molecules on the cancer cells' surface.

SBR Vulcanizates Filled with Modified Ground Tire Rubber.

Ground tire rubber (GTR) is used to decrease the cost of vulcanizates. However, insufficient interactions between GTR particles and rubber matrices make mechanical properties of vulcanizates containing GTR deteriorate. This paper compares original methods of GTR modification. The effects of surface activation of GTR by sulfuric acid (A), its modification by (3-mercaptopropyl)trimethoxy silane (M), or the hybrid treatment-combining both approaches (H), were analyzed in terms of surface energy, specific surface area and morphology of GTR particles. Vulcanizates containing virgin GTR were compared to the rubber filled with the modified GTR particles keeping the same amount of CB in the rubber mix, according to their crosslink density, mechanical and tribological properties. Contrary to the virgin GTR, the addition of modified GTR increases the stiffness of the vulcanizates. The highest changes have been observed for the samples filled with ca. 12 phr of the GTR modified with silane and ca. 25 phr of the GTR subjected to the hybrid treatment, representing the highest crosslink density of rubber vulcanizates filled with GTR. Furthermore, the addition of modified GTR, especially in the case of the samples where 10 phr of rubber was replaced, results in the significant lowering of friction but higher abrasive wear.

The influence of dielectric permittivity of water on the shape of PtNPs synthesized in high-pressure high-temperature microwave reactor.

In this paper, a novel method for the synthesis of Pt nanoparticles (PtNPs) using a microwave autoclave reactor is proposed. For benchmarking, the obtained results are compared with the traditional, batch method. A novel process window is proposed, which is the application of high-temperature and high-pressure. The main finding is that this only brings advantage, when the ionic strength of the system is enough low. It is explained, that at high pressure and high temperature, water behaves like only a slightly polar solvent, approaching a subcritical state. This reduces the electrostatic stabilization of the particles. Moreover, a change in the Pt particle shape is observed under high pressure and temperature conditions, suggesting that additional physical-chemical processes are involved.

Thermal Stability and Flammability of Styrene-Butadiene Rubber-Based (SBR) Ceramifiable Composites.

Ceramifiable styrene-butadiene (SBR)-based composites containing low-softening-point-temperature glassy frit promoting ceramification, precipitated silica, one of four thermally stable refractory fillers (halloysite, calcined kaolin, mica or wollastonite) and a sulfur-based curing system were prepared. Kinetics of vulcanization and basic mechanical properties were analyzed and added as Supplementary Materials. Combustibility of the composites was measured by means of cone calorimetry. Their thermal properties were analyzed by means of thermogravimetry and specific heat capacity determination. Activation energy of thermal decomposition was calculated using the Flynn-Wall-Ozawa method. Finally, compression strength of the composites after ceramification was measured and their micromorphology was studied by scanning electron microscopy. The addition of a ceramification-facilitating system resulted in the lowering of combustibility and significant improvement of the thermal stability of the composites. Moreover, the compression strength of the mineral structure formed after ceramification is considerably high. The most promising refractory fillers for SBR-based ceramifiable composites are mica and halloysite.

Three-dimensional microstructural characterization of porous cubic zirconia.

A set of cubic zirconia samples were investigated using 3-dimensional electron backscatter diffraction (3D EBSD) to analyze the grain structure, grain boundary networks and pore morphology. 3D EBSD is a variation of conventional EBSD, whereby a focused ion beam (FIB) is used in a dual beam scanning electron microscope (SEM) i.e. FIB-SEM to mill away material and to create 'serial sections' through the material being analyzed. Each new surface revealed is subject to an EBSD scan, which continues sequentially until a desired volume of material has been removed. In this manner, many consecutive 2D EBSD scans can be rendered in 3D to gain a greater insight of microstructural features and parameters. The three samples were examined in order to determine the effect of differences in the manufacturing process used for each. For each sample, a volume of ca. 15,000 µm(3) was studied. The analysis of several microstructure parameters revealed a strong dependence on manufacturing conditions. Subsequently, the results of 3D EBSD analysis were compared to conventional 2D EBSD. Significant differences between the values of microstructure parameters determined by 2D and 3D EBSD were observed.

The influence of the API properties on the ODTs manufacturing from co-processed excipient systems.

Directly compressible co-processed excipient systems facilitate orodispersible tablets (ODTs) manufacturing. Despite several excipient systems available, it is reported that the incorporation of high drug dose into the tablet mass may negatively affect both disintegration and mechanical properties. Therefore the influence of drug properties on the quality of orodispersible tablets was investigated. Fast dissolving tablet matrix was made of a co-processed excipient system F-Melt. Two grades of F-Melt that differed in composition, particle shape, and specific surface area were used to form tablet matrix. Ibuprofen, diclofenac sodium, and diltiazem hydrochloride were chosen as model drugs of different physicochemical properties such as solubility, particle size, and shape. Ninety formulations containing 12.5, 25, or 50 wt% of the model drug and F-Melt type C or M were prepared by direct compression. The quality of tablets was examined on the base of disintegration time, wetting time, mechanical resistance and texture analysis. The results showed that F-Melt grade, drug solubility, and its dose had an influence on the quality of tablets. From ninety formulations prepared, only four batches containing F-Melt type C and 12.5 wt% of ibuprofen, diclofenac sodium, or diltiazem hydrochloride could be classified as ODTs. Their disintegration time ranged from 41 to 144 s. In the case of F-Melt type M, tablets disintegrating within 101 s of friability below 1% could be prepared only if 12.5 wt% of diclofenac sodium was incorporated into the tablet mass.