Membrane fluidity properties of lipid-coated polylactic acid nanoparticles.

Lipid coating is considered a versatile strategy to equip nanoparticles (NPs) with a biomimetic surface coating, but the membrane properties of these nanoassemblies remain in many cases insufficiently understood. In this work, we apply C-Laurdan generalized polarization (GP) measurements to probe the temperature-dependent polarity of hybrid membranes consisting of a lipid monolayer adsorbed onto a polylactic acid (PLA) polymer core as function of lipid composition and compare the behavior of the lipid coated NPs (LNPs) with that of liposomes assembled from identical lipid mixtures. The LNPs were generated by nanoprecipitation of the polymer in aqueous solutions containing two types of lipid mixtures: (i) cholesterol, dipalmitoylphosphatidylcholine (DPPC), and the ganglioside GM3, as well as (ii) dioleoylphosphatidylcholine (DOPC), DPPC and GM3. LNPs were found to exhibit more distinct and narrower phase transitions than corresponding liposomes and to retain detectable phase transitions even for cholesterol or DOPC concentrations that yielded no detectable transitions in liposomes. These findings together with higher GP values in the case of the LNPs for temperatures above the phase transition temperature indicate a stabilization of the membrane through the polymer core. LNP binding studies to GM3-recognizing cells indicate that differences in the membrane fluidity affect binding avidity in the investigated model system.

Visible-Light Photoredox-Catalyzed Three-Component Reaction of Carbazoles with Alkenes and S-(Difluoromethyl)sulfonium Salt: A Practical Approach to Access Difluoroalkyl-Functionalized Carbazoles.

A mild and elegant multicomponent protocol for construction of CF2H-containing carbazoles was accomplished by visible-light photoredox catalysis with formation of two new C-C bonds in a single step to deliver a wide variety of structurally diverse difluoroalkylated carbazoles in moderate to good yields, featuring mild reaction conditions, synthetic simplicity, broad substrates, and good functional group tolerance.

Visible-light photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamides with S-(difluoromethyl)sulfonium salt.

A facile and highly efficient visible-light photoredox-catalyzed protocol for aryldifluoromethylation of acrylamides was developed using S-(difluoromethyl)sulfonium salt as the difluoromethyl source. With this method, pharmaceutically interesting CF2H-containing oxindoles were readily accessed from N-arylacrylamides, and this method featured mild reaction conditions, a broad scope of substrates, good tolerance of functional groups, and good to excellent yields. Control experiments revealed that this protocol proceeded through a difluoromethylation/cyclization cascade process.

Facile Entry to Pharmaceutically Important 3-Difluoromethyl-quinoxalin-2-ones Enabled by Visible-Light-Driven Difluoromethylation of Quinoxalin-2-ones.

CF2H moiety has a significant potential utility in drug design and discovery, and the incorporation of CF2H into biologically active molecules represents an important and efficient strategy for seeking lead compounds and drug candidates. On the other hand, quinoxalin-2-one is of great interest to pharmaceutical chemists as a common skeleton frequently occurring in plenty of natural products and bioactive compounds. Herein, we reported a practical and efficient protocol for the synthesis of 3-CF2H-quinoxalin-2-ones. Thus, in the presence of 3 mol% of photocatalyst and S-(difluoromethyl)sulfonium salt as difluoromethyl radical sources, a wide range of quinoxalin-2-ones readily underwent a visible-light redox-catalyzed difluoromethylation reaction, to deliver structurally diverse 3-difluoromethyl-quinoxalin-2-ones. We believe that this would facilitate increasing chances and possibilities for seeking potential lead compounds and drug candidates and further boost the development of fluorine-containing pharmaceuticals.

An electrochemiluminescence cytosensor for sensitive detection of HeLa cells based on a signal amplification strategy of Au-NaYF4:Yb,Er nanocomposites.

A novel electrochemiluminescence (ECL) cytosensor was proposed for the quantitative detection of HeLa cells (human cervical cancer cells) with the help of a signal amplification strategy. Firstly, the Au-NaYF4:Yb,Er nanocomposites were prepared by a simple in situ hydrothermal method and characterized by transmission electron microscopy (TEM) images, X-ray diffraction (XRD) patterns, UV-vis spectra and Fourier transform infrared (FTIR) spectra. Compared with the bare NaYF4:Yb,Er nanocomposites, the ECL intensity of Au-NaYF4:Yb,Er nanocomposites was greatly enhanced by about 4.2-fold which can be attributed to the good conductivity of gold nanoparticles (Au NPs). The nanocomposites showed high and stable ECL emission, fast response and superior conductivity, all of which were advantageous to the ECL detection. Furthermore, HeLa cells were immobilized on the modified electrode via the interaction between folic acid and a folate receptor present on the cell surface. The ECL cytosensor showed satisfactory sensitive response to HeLa cells in a linear range of 4.25 × 102-4.25 × 105 cells per mL with a low detection limit of 326 cells per mL. The proposed cytosensor had good sensitivity and stability, which can offer a great potential platform for bioassay analysis.

Tuning Wet Adhesion of Weak Polyelectrolyte Multilayers.

Weak polyelectrolyte multilayers (PEMs) assembled by the layer-by-layer method are known to become tacky upon contact with water and behave as a viscoelastic fluid, but this wet adhesive property and how it can be modified by external stimuli has not yet been fully explored. We present here a study on the wet adhesive performance of PEMs consisting of branched poly(ethylene imine) and poly(acrylic acid) under controlled conditions (e.g., pH, type of salt, and ionic strength) using a 90° peel test. The multilayers demonstrate stick-slip behavior and fail cohesively in nearly all cases. The peel force is the highest at neutral pH, and it decreases in both acidic/basic environments because of inhibited polyelectrolyte mobility. The addition of salts with various metal ions generally reduces the peel force, and this effect tracks with the ionic strength. When transition metal ions are used, their ability to form coordination bonds increases the peel force, with two exceptions (Cu2+ and Zn2+). With a transition metal ion such as Fe3+, the peel force first increases as a function of the concentration and then eventually decreases. The peel force increases proportionally to the peel rate. The films are also characterized via zeta potential (when assembled onto colloidal particles) and shear rheometry. This work provides insight into both the wet adhesive properties of PEMs and the interactions between PEMs and metal ions.

Accelerated Amidization of Branched Poly(ethylenimine)/Poly(acrylic acid) Multilayer Films by Microwave Heating.

Chemical cross-linking of layer-by-layer assembled films promotes mechanical stability and robustness in a wide variety of environments, which can be a challenge for polyelectrolyte multilayers in saline environments or for multilayers made from weak polyelectrolytes in environments with extreme pHs. Heating branched poly(ethylenimine)/poly(acrylic acid) (BPEI/PAA) multilayers at sufficiently high temperatures drives amidization and dehydration to covalently cross-link the film, but this reaction is rather slow, typically requiring heating for hours for appreciable cross-linking to occur. Here, a more than one order of magnitude increase in the amidization kinetics is realized through microwave heating of BPEI/PAA multilayers on indium tin oxide (ITO)/glass substrates. The cross-linking reaction is tracked using infrared spectroscopic ellipsometry to monitor the development of the cross-linking products. For thick films (∼1500 nm), gradients in cross-link density can be readily identified by infrared ellipsometry. Such gradients in cross-link density are driven by the temperature gradient developed by the localized heating of ITO by microwaves. This significant acceleration of reactions using microwaves to generate a well-defined cross-link network as well as being a simple method for developing graded materials should open new applications for these polymer films and coatings.

Response of Swelling Behavior of Weak Branched Poly(ethylene imine)/Poly(acrylic acid) Polyelectrolyte Multilayers to Thermal Treatment.

Weak polyelectrolyte multilayers (PEMs) prepared by the layer-by-layer technique have attracted a great deal of attention as smart responsive materials for biological and other applications in aqueous medium, but their dynamic behavior as a function of exposure to a wide temperature range is still not well understood. In this work, the thermally dependent swelling behavior of PEMs consisting of branched poly(ethylenimine) and poly(acrylic acid) is studied by temperature controlled in situ spectroscopic ellipsometry. Because of diffusion and interpenetration of polyelectrolytes during film deposition, the PEMs densify with increasing bilayer number, which further affects their water uptake behavior. Upon heating to temperatures below 60 °C, the worsened solvent quality of the PEM in water causes deswelling of the PEMs. However, once heated above this critical temperature, the hydrogen bonds within the PEMs are weakened, which allows for chain rearrangement within the film upon cooling, resulting in enhanced water uptake and increased film thickness. The current work provides fundamental insight into the unique dynamic behavior of weak polyelectrolyte multilayers in water at elevated temperatures.

Contraction of weak polyelectrolyte multilayers in response to organic solvents.

Weak polyelectrolyte multilayers (PEMs) prepared by the layer-by-layer assembly technique have recently been found to demonstrate a unique contraction upon exposure to organic solvents. This response is dependent upon which organic solvent is employed, and fundamental questions have not been clarified regarding the correlation of the magnitude of the film contraction with solvent type. In this work, we used solubility parameters to analyze the response of branched poly(ethylene imine)/poly(acrylic acid) (BPEI/PAA) multilayers when exposed to a variety of solvents. BPEI/PAA multilayers were immersed in a series of 16 different organic solvents and solvent mixtures. Immersion in organic solvent caused film dehydration and therefore contraction and also induced changes in the mechanical properties of PEMs. The film thickness was the best predictor of how a film swelled in water or contracted in organic solvent when using different batches of commercially available polyelectrolytes, rather than polyelectrolyte assembly pH conditions. The degree of film contraction was correlated with Hansen and Kamlet-Taft solubility parameters as well as solvent dielectric constant. In most cases, the hydrogen bonding ability of solvents is the primary factor to determine the magnitude of film contraction. For these solvents, increasing the temperature which corresponds to decreasing the strength of hydrogen bonding, also decreases the ability to dehydrate the films. For solvents that do not follow these trends with the strength of hydrogen bonding, a stronger correlation was found between contraction and dielectric constant, indicating that both traditional solvent quality arguments and electrostatics are important to understanding the contraction of PEMs in organic solvents.

Large-scale solvent driven actuation of polyelectrolyte multilayers based on modulation of dynamic secondary interactions.

Polyelectrolyte multilayers (PEMs), assembled from weak polyelectrolytes, have often been proposed for use as smart or responsive materials. However, such response to chemical stimuli has been limited to aqueous environments with variations in ionic strength or pH. In this work, a large in magnitude and reversible transition in both the swelling/shrinking and the viscoelastic behavior of branched polyethylenimine/poly(acrylic acid) multilayers was realized in response to exposure with various polar organic solvents (e.g., ethanol, dimethyl sulfoxide, and tetrahydrofuran). The swelling of the PEM decreases with an addition of organic content in the organic solvent/water mixture, and the film contracts without dissolution in pure organic solvent. This large response is due to both the change in dielectric constant of the medium surrounding the film as well as an increase in hydrophobic interactions within the film. The deswelling and shrinking behavior in organic solvent significantly enhances its elasticity, resulting in a stepwise transition from an initially liquid-like film swollen in pure water to a rigid solid in pure organic solvents. This unique and recoverable transition in the swelling/shrinking behaviors and the rheological performances of weak polyelectrolyte multilayer film in organic solvents is much larger than changes due to ionic strength or pH, and it enables large scale actuation of a freestanding PEM. The current study opens a critical pathway toward the development of smart artificial materials.

Precise size control over ultrafine rutile titania nanocrystallites in hierarchical nanotubular silica/titania hybrids with efficient photocatalytic activity.

Hierarchical-structured nanotubular silica/titania hybrids incorporated with particle-size-controllable ultrafine rutile titania nanocrystallites were realized by deposition of ultrathin titania sandwiched silica gel films onto each nanofiber of natural cellulose substances (e.g., common commercial filter paper) and subsequent flame burning in air. The rapid flame burning transforms the initially amorphous titania into rutile phase titania, and the silica gel films suppress the crystallite growth of rutile titania, thereby achieving nano-precise size regulation of ultrafine rutile titania nanocrystallites densely embedded in the silica films of the nanotubes. The average diameters of these nanocrystallites are adjustable in a range of approximately 3.3-16.0 nm by a crystallite size increment rate of about 2.4 nm per titania deposition cycle. The silica films transfer the electrons activated by crystalline titania and generate catalytic reactive species at the outer surface. The size-tuned ultrafine rutile titania nanocrystallites distributed in the unique hierarchical networks significantly improve the photocatalytic performance of the rutile phase titania, thereby enabling a highly efficient photocatalytic degradation of the methylene blue dye under ultraviolet light irradiation, which is even superior to the pure anatase-titania-based materials. The facile stepwise size control of the rutile titania crystallites described here opens an effective pathway for the design and preparation of fine-nanostructured rutile phase titania materials to explore potential applications.

Ultrathin cellulose film coating of porous alumina membranes for adsorption of superoxide dismutase.

The non-toxic and biocompatible cellulose possesses nonspecific binding properties for many protein molecules. But its abundant inter- and intra-molecular hydrogen bonds induce spontaneous self-assembly of cellulose into a random fibrous morphology and cellulose film coating is usually just available for two-dimensional flat substrates, which severely limits its protein adsorption performance. In this study, direct self-assembly of an ultrathin cellulose film on hybrid polyelectrolyte multilayer pre-coated pore surfaces of an anodic aluminum oxide membrane was achieved through the dissolution and precipitation of cellulose from N-methylmorpholine oxide solution. Each pore channel surface pre-coated with a uniform polyelectrolyte hybrid layer (thickness ∼5.0 nm) was covered by a cellulose film (∼15.0 nm) consisting of dense cellulose nanoparticles with a diameter of 5.5 ± 1.4 nm. The three-dimensional porous structure of the aluminum oxide membrane was well-preserved and micrometre-long flexible nanotubes with an average outer diameter of ∼200 nm were obtained after further aluminum oxide template dissolution treatment in an acidic environment. Moreover, the cellulose film coated pore channel surfaces presented sufficient hydrogen bonds and exhibited a high adsorption capacity rate of ∼1.45 mg m-2 for superoxide dismutase. This facile cellulose deposition approach enabled ultrathin cellulose film coating on three-dimensional structured substrates for enhanced adsorption performance for protein molecules.

Flame synthesis of hierarchical nanotubular rutile titania derived from natural cellulose substance.

Hierarchical nanotubular rutile titania material was fabricated by facile flame burning of ultrathin titania gel film coated cellulose nanofibres of commercial cellulose substance (filter paper), which possesses efficient photocatalytic performance for degradation of organic dye (methylene blue) under ultraviolet irradiation.

Superparamagnetic hierarchical material fabricated by protein molecule assembly on natural cellulose nanofibres.

Bio-inspired superparamagnetic hierarchical material which possesses significant thermal stability and superparamagnetic property was fabricated by core reconstruction of silica thin film coated ferritin molecules that were immobilized on the surface of natural cellulose nanofibres of common commercial filter paper.

Hierarchical, titania-coated, carbon nanofibrous material derived from a natural cellulosic substance.

Hierarchical, titania-coated, nanofibrous, carbon hybrid materials were fabricated by employing natural cellulosic substances (commercial filter paper) as a scaffold and carbon precursor. Ultrathin titania films were firstly deposited by means of a surface sol-gel process to coat each nanofiber in the filter paper, and successive calcination treatment under nitrogen atmosphere yielded the titania-carbon composite possessing the hierarchical morphologies and structures of the initial paper. The ultrathin titania coating hindered the coalescence effect of the carbon species that formed during the carbonization process of cellulose, and the original cellulose nanofibers were converted into porous carbon nanofibers (diameters from tens to hundreds of nanometers, with 3-6 nm pores) that were coated with uniform anatase titania thin films (thickness approximately 12 nm, composed of anatase nanocrystals with sizes of approximately 4.5 nm). This titania-coated, nanofibrous, carbon material possesses a specific surface area of 404 m(2) g(-1), which is two orders of magnitude higher than the titania-cellulose hybrid prepared by atomic layer deposition of titania on the cellulose fibers of filter paper. The photocatalytic activity of the titania-carbon composite was evaluated by the improved photodegradation efficiency of different dyes in aqueous solutions under high-pressure, fluorescent mercury-lamp irradiation, as well as the effective photoreduction performance of silver cations to silver nanoparticles with ultraviolet irradiation.

Transport characteristics of candesartan in human intestinal Caco-2 cell line.

The intestinal absorptive characteristics and the efflux mechanisms of candesartan (CDS), a novel angiotensin II type 1 receptor blocker, were investigated. The Caco-2 cells were used as models of the intestinal mucosa to assess uptake and transport of CDS. The determination of CDS was performed by HPLC-Flu. In the Caco-2 cells, the uptake and absorptive transport of CDS were pH-independent (in the pH range 6.0-8.0). Passive membrane diffusion dominates the absorptive transport behavior of CDS across Caco-2 cells, while secretory transport was a concentration-dependent and saturable process. In the presence of cyclosporin A and verapamil, potent inhibitors of P-glycoprotein (P-gp), the P(ratio) decreased from 3.8 to 2.3 and 1.8, respectively, and permeation of apical to basolateral was enhanced. Overall, the current study suggests that efflux transporters are capable of mediating the absorption and secretion of CDS, and they may play significant roles in limiting the oral absorption of CDS.