Preparation of highly dispersible and tumor-accumulative, iron oxide nanoparticles Multi-point anchoring of PEG-b-poly(4-vinylbenzylphosphonate) improves performance significantly

This paper describes the preparation of iron oxide nanoparticles, surface of which was coated with extremely high immobilization stability and relatively higher density of poly(ethylene glycol) (PEG), which are referred to as PEG protected iron oxide nanoparticles (PEG-PIONs). The PEG-PIONs were obtained through alkali coprecipitation of iron salts in the presence of the PEG-poly(4-vinylbenzylphosphonate) block copolymer (PEG-b-PVBP). In this system, PEG-b-PVBP served as a surface coating that was bound to the iron oxide surface via multipoint anchoring of the phosphonate groups in the PVBP segment of PEG-b-PVBP. The binding of PEG-b-PVBP onto the iron oxide nanoparticle surface and the subsequent formation of a PEG brush layer were proved by FT-IR, zeta potential, and thermogravimetric measurements. The surface PEG-chain density of the PEG-PIONs varied depending on the [PEG-b-PVBP]/[iron salts] feed-weight ratio in the coprecipitation reaction. PEG-PIONs prepared at an optimal feed-weight ratio in this study showed a high surface PEG-chain surface density (≈0.8 chainsnm(-2)) and small hydrodynamic diameter (<50 nm). Furthermore, these PEG-PIONs could be dispersed in phosphate-buffered saline (PBS) that contains 10% serum without any change in their hydrodynamic diameters over a period of one week, indicating that PEG-PIONs would provide high dispersion stability under in vivo physiological conditions as well as excellent anti-biofouling properties. In fact we have confirmed the prolong blood circulation time and facilitate tumor accumulation (more than 15% IDg(-1) tumor) of PEG-PIONs without the aid of any target ligand in mouse tumor models. The majority of the PEG-PIONs accumulated in the tumor by 96 h after administration, whereas those in normal tissues were smoothly eliminated by 96 h, proving the enhancement of tumor selectivity in the PEG-PION localization. The results obtained here strongly suggest that originally synthesized PEG-b-PVBP, having multipoint anchoring character by the phosphonate groups, is rational design for improvement in nanoparticle as in vivo application. Two major points, viz., extremely stable anchoring character and dense PEG chains tethered on the nanoparticle surface, worked simultaneously to become PEG-PIONs as an ideal biomedical devices intact for prolonged periods in harsh biological environments.     

Ultraviolet-A irradiation to the eye modulates intestinal mucosal functions and properties of mast cells in the mouse

We previously reported that topical irradiation of the eye by ultraviolet-B (UVB) activated hypothalamo-pituitary-adrenal axis (HPA-A) of the mouse to increase 3, 4-dihydroxyphenylalanine (DOPA)-positive melanocytes in the skin by an inducible nitric oxide synthase (iNOS)-dependent mechanism. This work demonstrates that irradiation of the eye by ultraviolet-A (UVA) specifically increased DOPA-positive cells in the mucosa of the jejunum and colon of C57BL/6J mice by some HPA- and iNOS-independent mechanism. UVA-induced increase in DOPA-positive cells in the intestine was inhibited by the administration of hexamethonium or prazosin plus propranolol, blockers for the sympathetic nervous system. UVA irradiation of the eye increased DOPA- and histidine decarboxylase (HDC)-positive cells in the intestinal mucosa of both C57BL/6J and WBB6F1/J mice but not in the mutant strain W/Wv of the latter that lack mast cells. UVA irradiation of the eye suppressed the intestinal peristalsis of control, hypophysectomized or iNOS(-/-) C57BL/6J mice by the mechanism that was inhibited by hexamethonium or prazosin plus propranolol. These observations suggest that UVA irradiation of the eye stimulated the sympathetic nervous system to increase the mucosal DOPA- and HDC-positive mast cells and suppressed the peristalsis of the small intestine of the mouse.     

Phosphoproteome Profiling Using a Fluorescent Phosphosensor Dye in Two-Dimensional Polyacrylamide Gel Electrophoresis

We validated the novel PhosphoQUANTI SolidBlue Complex (PQSC) dye for the sensitive fluorescent detection of phosphorylated proteins in polyacrylamide- and two-dimensional gel electrophoresis (PAGE and 2DE, respectively). PQSC can detect as little as 15.6 ng of ß-casein, a pentaphosphorylated protein, and 61.3 ng of ovalbumin, a diphosphorylated protein. Fluorescence intensity correlates with the number of phosphorylated residues on the protein. To demonstrate the specificity of PQSC for phosphoproteins, enzymatically dephosphorylated lysates of Swiss 3T3 cells were separated in 2DE gels and stained by PQSC. The fluorescence signals in these gels were markedly reduced following dephosphorylation. When the phosphorylated proteins in Swiss 3T3 cell lysates were concentrated using a phosphoprotein enrichment column, the majority of phosphoproteins showed fluorescence signals in the pI 4–5 range. Finally, we performed phosphoproteome analysis to study differences in the protein phosphorylation profiles of proliferating and quiescent Swiss 3T3 cells. Over 135 discernible protein spots were detected, from which a selection of 15 spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF-MS). The PQSC staining procedure for phosphoprotein detection is simple, reversible, and fully compatible with MALDI TOF-MS.     

Evolution of packing parameters in the structural changes of silica mesoporous crystals: cage-type, 2D cylindrical, bicontinuous diamond and gyroid, and lamellar

Cage-type, two-dimensional (2D) cylindrical hexagonal (C), bicontinuous diamond (D), bicontinuous gyroid (G), and one-dimensional (1D) lamellar (L) structures of silica mesoporous crystals (SMCs) were obtained by using the anionic surfactant N-stearoyl-l-glutamic acid (C(18)GluA) as a template in the presence of the nonionic surfactant C(16)(EO)(10) (Brij-56). The mesostructures were controlled by the organic/inorganic interface curvature change induced by Brij-56. A synthesis-field diagram showed that the mesostructure changed in the sequence cage-type → C → intergrowth of C and D → intergrowth of C and G → D → G → L with increase of the amount of Brij-56. Mixed micelles were formed by the anionic and nonionic surfactants, the packing parameter g of which increased with increasing the addition amount of nonionic surfactant and the reaction temperature. The local g parameter was obtained from electron crystallography reconstruction results by calculating mean curvatures and Gaussian curvatures from the equi-electrostatic potential surface. The intergrowth of C and D and two kinds of intergrowth of C and G are also discussed.     

Synthesis and characterization of benzo[1,2-b:3,4-b':5,6-b']trithiophene (BTT) oligomers

Two dimers (2 and 3), dendritic tetramer (4), hexamer (5), and decamer (6) of benzo[1,2-b:3,4-b':5,6-b']trithiophene (BTT), a potential π-core unit with C(3h) symmetry, were synthesized, characterized, and evaluated for possible use as organic semiconductors. Single crystal X-ray analyses of the dimers (2 and 3) revealed that they have planar molecular structures with dihedral angles of almost 180° between two BTT units. In accordance with the rigid and planar molecular structure, the unsubstituted dimer (2) is poorly soluble, whereas the octyl-substituted dimer (3) has improved solubility. Although the solubility of the dendritic tetramer (4) is decreased, further extended systems, i.e., the dendritic hexamer (5) and decamer (6), have solubilities better than that of 4. With increasing numbers of BTT units in the molecule, the experimentally determined energy levels of HOMO shift upward slightly and the HOMO-LUMO energy gaps become smaller, but the extent of HOMO destabilization and reduction of the HOMO-LUMO gap are not significant. Taking into account the energy levels of the frontier orbitals, 3-6 could be useful as p-channel organic semiconductors rather than n-channel. In fact, the spin-coated thin film of 3 with edge-on molecular orientation acted as an active channel of field-effect transistors that showed hole mobilities as high as 0.14 cm(2) V(-1) s(-1), indicating that the BTT core is a useful π-conjugated system for application to organic semiconductors, although 4-6 gave FET characteristics rather inferior to those of 3, owing to their amorphous nature in the thin film state.     

Linking Conformational Flexibility and Kinetics: Catalytic 1,4‐Type Friedel–Crafts Reactions of Phenols Utilizing 1,3‐Diamine‐Tethered Guanidine/Bisthiourea Organocatalysts

Herein, we present details of our conformationally flexible, 1,3‐diamine‐tethered guanidine/bisthiourea organocatalysts for chemo‐, regio‐, and enantioselective 1,4‐type Friedel–Crafts reactions of phenols. These organocatalysts show a unique stereo‐discrimination governed by the differential activation entropy (ΔΔS^≠), rather than by the differential activation enthalpy (ΔΔH^≠). Extensive kinetic analyses using Eyring plots for a series of guanidine/bisthiourea organocatalysts revealed the key structural motif in the catalysts associated with a large magnitude of differential activation entropy (ΔΔS^≠). A plausible guanidine–thiourea cooperative mechanism for the enantioselective Friedel–Crafts reaction is proposed.     

Color Center Laser–Microwave Double Resonance Spectroscopy of the ν1Vibrational State of HCCF

Rotational transitions of fluoroacetylene in the ν₁(CH stretch) vibrational state have been observed by the laser–microwave double resonance technique using a color center laser as a radiation source in the 3 μm region. The rotational constant and centrifugal distortion constant in the ν₁state were determined to be 9684.310(16) MHz and 2.68(62) kHz, respectively, where the uncertainties given in parentheses correspond to 2.5 standard deviations.     

Liquid-liquid extraction of silver ion with benzothiacrown ether derivatives

The extraction behavior of mono-, poly-, anal bis-(benzothiacrown ether)s is studied for alkali, alkaline-earth, heavy, and transition metal ions in the presence of picrate. These ethers show high selectivity for silver ion. Silver extractions from binary and quaternary mixtures of silver with heavy or transition metal ions were successful, except for mixtures with mercury(II) ion. Silver was extracted from a copper ore with ca. 80% recovery.