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We demonstrate a successful target gene knockdown in ex vivo normal human bronchial epithelium (NHBE) cells covered with mucus layers using the guanylurea functionalization technique modulating the chemical environment at the positive charge of a gene carrier.

Bacterial infections are serious health threats. Emerging drug resistance in bacteria further poses serious challenges to the treatment options involving traditional antibiotics. Antimicrobial polymers disrupt the physical cell membrane integrity of bacteria to address the drug resistance problems. Here, we introduce a conceptually new class of antimicrobial polymers containing positively charged guanylurea backbones for enhanced antimicrobial effects. The initial structure-activity relationship studies demonstrate that poly(guanylurea piperazine)s (PGU-Ps) exhibit excellent antimicrobial activity against different types of bacteria with high selectivity. The new design concept of using a positively charged guanylurea backbone will contribute to the development of future biocompatible, specific, and selective antimicrobial polymers.

Melt viscosity control of polyamides is an important issue concerning polymer processing and quality composites which are directly influenced by the melt viscosity in extrusion and injection molding processes. In this work, a series of linear and cyclic PA6 (nylon6), PA46 (nylon46), and PA66 (nylon66)-based amide oligomers consisting of 30%. This result suggests that proper hydrogen bonding mismatching in the polymer chain network plays an important role for lowering viscosity. A6-L/PA66 composites impregnated with 40 wt% glass fiber show a twofold increase in the melt flow index while maintaining their mechanical strengths.

In-depth understanding of the biophysicochemical interactions at the nano-bio interface is important for basic cell biology and applications in nanomedicine and nanobiosensors. Here, the extracellular surface potential and topography changes of live cell membranes interacting with polymeric nanomaterials using a scanning ion conductance microscopy-based potential imaging technique are investigated. Two structurally similar amphiphilic conjugated polymer nanoparticles (CPNs) containing different functional groups (i.e., primary amine versus guanidine) are used to study incubation time and functional group-dependent extracellular surface potential and topographic changes. Transmembrane pores, which induce significant changes in potential, only appear transiently in the live cell membranes during the initial interactions. The cells are able to self-repair the damaged membrane and become resilient to prolonged CPN exposure. This study provides an important observation on how the cells interact with and respond to extracellular polymeric nanomaterials at the early stage. This study also demonstrates that extracellular surface potential imaging can provide a new insight to help understand the complicated interactions at the nano-bio interface and the following cellular responses.

A series of flexible, highly bright fluorescent poly(p-phenyleneethynylene)s (PPEs) was prepared by employing a disulfide containing nonconjugated monomer at various ratios under Sonogashira reaction conditions. PPEs with flexible linkers exhibited fluorescence properties comparable to those of a fully conjugated PPE when less than 50% of flexible monomers were incorporated into the backbone. To evaluate the self-assembly properties of PPEs, a series of conjugated polymer nanoparticles (CPNs) was fabricated by treating PPEs with organic acids followed by dialysis. CPNs containing linkers exhibited different complexation behavior with polysaccharides, warranting further investigation into how flexibility and biodegradability of CPNs influence their cellular interaction and entry. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1403–1412

Copper-catalyzed coupling reaction of 2-io- dobenzoic acids and alkynes such as terminal acety- lenes, alkynyl carboxylic acids, and trimethylsilylace- tylene selectively afforded isocoumarins and phthal- A in the presence of cesium carbonate (Cs2CO3) and dimethyl sulfoxide (DMSO). Among the regio- selective products, only the 6-endo-dig product, iso- coumarin, was formed at 1008C, and the 5-exo-dig product, phthalide, was formed as a major product at 258C. A variety of alkynes produced the correspond- ing isocoumarins and phthalides in good yields. A mechanism is suggested in which the formation of 2- alkynylbenzoic acid as an intermediate via Sonoga- shira-type coupling was ruled out in the reaction pathway.

Core-shell conjugated polymer nanoparticles (CPNs) were fabricated by complexing a semi-flexible, primary amine-containing conjugated polymer (CP) with hyaluronic acid (HA). Flexibility introduced in the rigid rod conjugated backbone allows backbone reorganization to increase π-π interaction under ionic complexation, resulting in core-shell nanoparticles with a hydrophobic CP core wrapped with a HA shell. The core-shell nanoparticles exhibited no cellular toxicity and high cancer cell specificity with minimal binding to normal cells.

Conjugated random copolymers containing phenylene­butadiynylenes and phenyleneethynylenes were synthesized from the palladium- and copper-catalyzed decarboxylative coupling reaction of propiolic acid with aryl iodides. This one-step synthetic approach provides a facile route to conjugated polymers whose synthesis typically requires a multistep conversion of the starting diiodoarenes into diacetylenes prior to polymerization.

Understanding the cellular entry pathways of synthetic biomaterials is highly important to improve overall labeling and delivery efficiency. Herein, cellular entry mechanisms of conjugated polymer nanoparticles (CPNs) are presented. CPNs are intrinsic fluorescent materials used for various biological applications. While CPNs cause no toxicity, decreased CPN uptake is observed from cancer cells pretreated with genistein, which is an inhibitor of caveolae-mediated endocytosis (CvME). CvME is further confirmed by high co-localization with caveolin-1 proteins found in the caveolae and caveosomes. Excellent photophysical properties, non-toxicity, and non-destructive delivery pathways support that CPNs are promising multifunctional carriers minimizing degradation of contents during delivery.

We developed a new synthetic approach to high molecular weight poly(p-phenylenebutadiynylene) s (PPBs) by increasing backbone flexibility. The introduction of a small amount of flexible units along the backbone improved both the physical and photophysical properties of the polymers. These materials were successfully fabricated into conjugated polymer nanoparticles (CPNs) and used for fluorescent live cell imaging for the first time.

Biodegradable conjugated polymer nanoparticles (CPNs) were prepared for high mitochondrial targeting in live cancer cells. The degradable CPNs are nontoxic and specifically localized to the mitochondria of live tumor cells through macropinocytosis followed by intracellular degradation and trafficking.

Understanding and controlling aggregation structures of conjugated polymers (CPs) in aqueous solutions is critical to improving the physical and photophysical properties of CPs for biological applications. Here, we present spectroscopic evidence, including nuclear magnetic resonance (NMR) spectroscopic results, that different organic acid treatment induces different aggregation structures and photophysical properties of CPs in water. Conjugated polymer nanoparticles (CPNs) were fabricated by treating a non-aqueous soluble, primary amine-containing poly(phenylene ethynylene) (PPE-NH(2)) with organic acids followed by dialysis. CPNs formed by acetic acid (AA) treatment (CPN-AAs) exhibit characteristics of loose aggregation with minimal π-π stacking, while CPNs formed by tartaric acid (TA) treatment (CPN-TAs) exhibit a high degree of π-π stacking among PPE-NH(2) chains. The controlled aggregation for a specific application was demonstrated by comparing the fluorescence quenching abilities of the CPN-AAs and the CPN-TAs. A doubled Stern-Volmer constant was obtained from the densely packed CPN-TAs compared to that of the loosely aggregated CPN-AAs.

Positively charged conjugated polymer nanoparticles (CPNs) are emerging biomaterials exhibiting high levels of cellular entry. High rate of cellular entry efficiency is believed that the amphiphilic CPNs interact efficiently with the negatively charged hydrophobic cellular membranes. For the first time, the cell surface morphological changes of human cervical cancer cells treated with CPNs using a scanning probe microscopy technique, scanning ion conductance microscopy (SICM) are imaged. After 1 h of CPN incubation, distinct changes are observed in cell surface morphology such as interconnected protrusions and pits with sub-micrometer sizes, which are not observed from cells treated with positively charged polyethyleneimine (PEI) under the same treatment conditions. The change on cell surface morphology is quantified by surface roughness ratio, which is increased as CPN concentration increases, while the ratio first increases and then decreases as the incubation time increases. These results suggest that cells respond actively toward CPN with both positive charges on the side chain and the hydrophobicity from rigid aromatic backbone, which leads to subsequent endocytosis. In conclusion, it is demonstrated that SICM is a suitable imaging technique to reveal the dynamic alternations on the cell surface morphology at the early stage of nanoparticles endocytosis with high resolution.

Thin films of Bi2O3-ZnO-Nb2O5 system with cubic pyrochlore structure can be deposited using both cubic and monoclinic (zirconolite) targets. When monoclinic target was used, the as-deposited phase was nonequilibrium cubic monophase. After post-annealing in the 600–800^∘C range, phase decomposition occurred, resulting in more thermodynamically stable cubic pyrochlore and monoclinic zirconolite phases. The dielectric properties, such as dielectric constant and electric field dependent tunability, showed a steep increase along with phase separation. However, dielectric loss had a reverse tendency. The maximum tunability was about 38%, which exceeds that of cubic pyrochlore monophase films deposited from cubic target.

Aminosilylated surface was treated with halide-substituted aromatic aldehydes, and the resulting molecular layers were examined with synchrotron X-ray photoelectron spectroscopy at the 2B1 SGM and 4B1 microscopy beamline in the Pohang Accelerator Laboratory. It was observed that the halide group of the film diminished upon the irradiation, but the other bands were constant in terms of the intensity and the shape. This observation indicates that the functional groups of the organic monolayers are cleaved selectively by soft X-rays. The cleavage rate was measured as a function of photon energy and normalized with photon flux. The cleavage is first-order to the concentration of the functional group. Its rate constant is sensitive to the molecular structure of the organic monolayers and the kind of substituents on the aromatic ring.

Optimized conditions are developed for the coupling reaction of 2-iodobenzoic acid with various alkynes.

The surface of a fused silica and oxidized silicon wafer (SiO2/Si(100)) was treated with (3-aminopropyl)triethoxysilane (1), (3-aminopropyl)diethoxymethylsilane (2), and (3-aminopropyl)ethoxydimethylsilane (3) for 72 h in solution. Thickness of the aminosilylated film out of 1 increases rapidly, and it turns out to be around 100 A in 72 h. Rather slow increase of the thickness is observed for 2, which produces the layers of 8 and 14 A in 10 and 72 h, respectively. The reagent 3 produces the monolayers of constant thickness 7−8 A during the whole span of the reaction. The aminosilane layer was allowed to react with 4-nitrobenzaldehyde to form an imine, and absorbance (Asurf) of the imine was recorded by UV−vis spectroscopy. The imine was hydrolyzed in a known volume of water to produce 4-nitrobenzaldehyde, and subsequently its absorbance was measured. Thus observed number of the aldehyde molecules is equivalent to the number of the imine molecules on the surface. With the known surface area of the substrat...

The surface of a fused silica and oxidized silicon wafer (SiO2/Si(100)) was treated with (4-aminophenyl)trimethoxysilane (1), (3-aminopropyl)triethoxysilane (2), (3-aminopropyl)diethoxymethylsilane (3), and (3-aminopropyl)ethoxydimethylsilane (4) in solution. The thickness of thus formed aminosilane layers was determined with ellipsometry. In most cases silane coupling agents produce monolayers of 6−10 A thickness, but reagent 2 gives multilayers with variable thickness (6−100 A) depending upon the dipping time. The aminosilane layers were allowed to react with 4-nitrobenzaldehyde, and formation of the corresponding imines was confirmed by UV−vis spectroscopy. Relative surface density of the amines was calculated from the observed absorbance. In aqueous medium the imines were easily hydrolyzed to regenerate the amine group. The process, the formation, and the subsequent hydrolysis of the imines, can be repeated several times without any noticeable degradation of the absorption characteristics. The ellipso...

Loosely aggregated conjugated polymer nanoparticles (CPNs) were used as nontoxic and efficient small interfering RNA (siRNA) delivery vehicles with delivery visualization. A significant down regulation (94%) of a target gene was achieved by transfection of HeLa cells with the CPNs/siRNA complexes, supporting CPN as a promising siRNA delivery carrier.

Aminosilylated substrate was treated with aziridines in order to prepare hyperbranched polymers on solid supports such as silicon wafer and fused silica. It is observed that the primary amine on the substrate is good enough to initiate the ring-opening polymerization of aziridine. Measuring the thickness of the film and the absolute density of the primary amine functionality shows that a very highly branched poly(ethyleneimine) is formed upon the reaction. The surface density of the primary amine functional group (-NH(2)) on the very top surface increased dramatically (from 3.5 amines/nm(2) to 66 amines/nm(2)). A protected aziridine, benzyl 1-aziridinecarboxylate, was employed for the stepwise growth of the film. Two step-processes, chain growth and deprotection, were successful in growing the molecular layer, and a linear chain was formed without branching. Copyright 2000 Academic Press.

Decarboxylative coupling of sp-sp2 carbons is possible by palladium catalyst. Employing propiolic acid (1) as a difunctional alkyne, and using the consecutive reactions of the Sonogashira reaction and the decarboxylative coupling, unsymmetrically substituted diaryl alkynes were obtained in moderate to good yield.

Fabrication, characterization, and application of poly(phenylene ethynylene) (PPE)/silica composite particles are described. PPE is a class of conjugated polymers, which has been used for various sensory materials. However, its hydrophobic nature makes its application difficult in the aqueous phase, especially for biological substance detection. In this report, we utilized non-aqueous soluble PPE, 15 nm of colloidal silica particles, and aminosilane to fabricate a biosensory platform. The resulting composite showed high aqueous compatibility, large surface area, high quantum efficiency, and versatile chemical modification including oligonucleotide coupling. By monitoring the fluorescence quenching of PPE, we could detect a quencher-labeled target oligonucleotide specifically. Stern-Volmer (SV) analysis showed different accessibility of fluorophores (PPE) to a quencher labeled target oligonucleotide. The accessibility of fluorophores and SV constant are determined to be 0.54 and 4.2 x 10(7)M(-1), respectively, from a modified SV plot. This method will broaden the capability of conjugated polymers for the sensitive detection of biological substances.

Sensors that are exceptionally sensitive with real-time outputs and minimal consumption of reagents are needed to continuously monitor air and water against bioterrorist incidents. Amplifying fluorescent polymers (AFP) provide exceptionally sensitive real-time reagentless sensor platforms as applied to detection of nitroaromatic explosives. This platform technology has the potential to be adapted to detect biological warfare (BW) agents by covalently attaching the 5’ end of stem-loop molecular beacons to AFP as DNA hybridization signal transduction switches. Molecular beacons with loop sequences specific for sequence signatures of a target BW agent are configured with a quencher on the end of the 3’ arm of the stem-loop. The AFP is quenched in the absence of target DNA, but upon hybridization with target the stem is melted, the duplex loop extended, and the AFP dequenched. This signal transduction is reversible upon removal of the target sequence with the molecular beacon reforming the stem-loop conformation. Proof-of-concept research has demonstrated that molecular beacons for signature sequences of Francisella tularensis result in correct identification of the presence of this agent in samples, but no false positives were seen with Escherichia coli.

Fluorescence quenching of poly(phenylene ethynylene) (PPE) particles by a Cy-5 labeled oligonucleotide is 2 orders of magnitude more sensitive than direct excitation of the Cy-5 fluorophore.

The subcellular localizations and toxicity of conjugated polymer nanoparticles (CPNs) are dependent on the chemical structure of the side chain and backbone structures. Primary amine-containing CPNs exhibit high Golgi localization with no toxicity. Incorporation of short ethylene oxide and tertiary amine side chains contributes to decreased Golgi localization and increased toxicity, respectively.

We have prepared two kinds of panels with a change in the sealing atmosphere. for this, air and nitrogen gas were used, respectively. The discharge voltages, Vfxy and Vfay, for the panel sealed in nitrogen gas were 35V and 30V lower, respectively, than those for the panel sealed in air. Moreover, long-term operation drifts in brightness, discharge voltage and delay time were considerably reduced. In order to find probable explanations to the differences caused by the sealing atmosphere, the protective layers were examined with analysis tools like SEM, CL and XPS. From this analysis, no clear explanation was obtained.

The ionic attraction was applied to construct nonlinear optical (NLO) chromophoric layers. In order to fully utilize such an interaction, stilbene-type NLO chromophores having an anionic group at one end of the chromophores were designed. Among such type of the chromophores, trans-4′-(4-sulfonic acid sodium salt)butanoxystyrylpyridine ( 1 ) was synthesized. The pyridine moiety of the chromophore can be easily methylated to augment the molecular hyperpolarizability (β). The above anionic chromophore self-assembles on the cationic surface, which is prepared by treating clean fused silica surface with 3-aminopropyltriethoxysilane and subsequently iodomethane. Characteristics of the molecular layer have been examined with contact angle measurement, UV-Vis spectroscopy, grazing-angle FTIR spectroscopy, and NLO property measurement.

Ionic attractions were applied to the construction of non-linear optical (NLO) chromophoric monolayers. In order to fully utilize such an interaction, stilbene-type NLO chromophores having a long alkyl chain and an anionic group at one end of the chain were designed; of this family of chromophores, sodium 11-[4-(trans-4′-pyridylstyryl)oxy] undecan-1-yl sulfate (3) was synthesized. By allowing a few minutes, this anionic chromophore self-assembles successfully on a cationically charged surface, which is prepared by treating clean fused silica with 3-aminopropyltriethoxysilane and then with iodomethane. The pyridine moiety of the self-assembled chromophore can be methylated to augment the molecular hyperpolarizability, β. The characteristics of the monolayer were examined viacontact angle measurements, UV–VIS spectroscopy, grazing-angle FTIR spectroscopy, and NLO property measurements.

A synchrotron radiation source was utilized for X-ray photoelectron spectroscopic analysis of a nitrobenzaldimine-formed monolayer. The N(1s) peak intensity for the nitro group becomes reduced upon X-ray irradiation, while C(1s) and O(1s) peaks are invariant. This observation indicates that the nitro group is cleaved selectively, leaving the phenyl ring intact in the layer. The cleavage rate is measured as a function of photon energy and normalized with the photon flux. The cleavage is first-order to the concentration of the nitro group. The rate constant is independent of the incident photon energy, suggesting that the cleavage is not associated with a direct photoexcitation of atomic core electrons. Electrons ejected by the X-ray are proposed as the most viable cause for the bond cleavage. The molecules remaining on the irradiated surface were analyzed with gas chromatography−mass spectrometry coupled with the solid-phase microextraction method after hydrolyzing the imine bond. It is found that the amou...

The surface of a fused silica and oxidized silicon wafer (SiO2/Si(100)) was treated with (3-aminopropyl)triethoxysilane in solution. The silane coupling agent (SCA) produces multilayers with variable thickness (6-100 A) depending upon the dipping time. The aminosilane layers were allowed to react with 4-nitrobenzaldehyde, and formation of the corresponding imine was confirmed by UV-vis spectroscopy. In aqueous medium the imine was easily hydrolyzed to regenerate the amine group and the aldehyde. Surface density of the amine was calculated from the amount of produced 4-nitrobenzaldehyde. Tilt angles of the chromophore, the imine, obtained from the surface density and Asurf, absorbance of the derivatized substrate, are 23-32°.