Poly Molecules Research Articles

Efficient sonodynamic ablation of deep-seated tumors via cancer-cell-membrane camouflaged biocompatible nanosonosensitizers

Ultrasound (US)-triggered therapies are promising in cancer treatments, and their effectiveness can be enhanced through the proper camouflage of sonosensitizers. Herein, we have constructed cancer cell membrane (CCM)-camouflaged sonosensitizers for homotypic tumor-targeted sonodynamic therapy (SDT). The camouflaged sonosensitizers have been prepared by encapsulating hemoporfin molecules in poly(lactic acid) polymers (H@PLA) and extruding with CCM from Colon Tumor 26 (CT26) cells, forming the H@PLA@CCM. Under excitation with US, the hemoporfin encapsulated in H@PLA@CCM can convert O2 into cytotoxic 1O2, which exerts an efficient sonodynamic effect. The H@PLA@CCM nanoparticles show enhanced cellular internalization to CT26 cells compared to H@PLA, and they also can be more efficiently engulfed by CT26 cells than by mouse breast cancer cells, due to the homologous targeting ability of CT26 CCM. After the intravenous injection, the blood circulation half-life of H@PLA@CCM is determined to be 3.23 h which is 4.3-time that of H@PLA. With high biosafety, homogeneous targeting ability, and sonodynamic effect, the combination of H@PLA@CCM and US irradiation has induced significant apoptosis and necrosis of tumor cells through the efficient SDT, achieving the strongest inhibition rate of tumors among other groups. This study provides insights into designing efficient and targeted cancer therapies using CCM-camouflaged sonosensitizers.

Exploring the Size Effect of Graphene Oxide on Crystallization Kinetics and Barrier Properties of Poly(lactic acid).

Two different sizes of graphene oxide/poly(lactic acid) composites were prepared by the solution flocculation method, and the effect of the size effect of graphene oxide on the crystallization, barrier, and mechanical properties of poly(lactic acid) was investigated by various characterization methods. The results of the crystallization behavior test show that the size change of graphene oxide has little effect on the nucleation effect of poly(lactic acid). Increasing the size of graphene oxide can promote the crystal growth, so as to improve the crystallization ability of poly(lactic acid). The test results of mechanical properties and barrier properties show that increasing the size of graphene oxide can provide a larger interfacial surface area and transmit stress more effectively, which can greatly improve the modulus of poly(lactic acid). At the same time, because of this, the diffusion path of gas molecules in poly(lactic acid) can be longer and more tortuous, so as to improve the barrier performance of poly(lactic acid).

Interactions of Ag Particles Stabilized by 7,7,8,8-Tetracyanoquinodimethane with Olefin Molecules in Poly(ether-block-amide).

In this study, to use a stabilized carrier, silver nanoparticles (AgNPs) were used as carriers and electron acceptors were added to activate the surface of AgNPs as olefin carriers. In addition, poly(ether-block-amide) (PEBAX), consisting of polyamide (hard segments) and polyether (soft segments), was investigated for the correlation of the between-segments ratio related to the stability of AgNPs and separation performance. As a result, contrary to the expectation that high permeance would be observed in PEBAX-1657/AgNPs/7,7,8,8-tetracyanoquinodimethane (TCNQ) membrane, which had a higher ratio of polyether soft segment, the PEBAX-5513/AgNPs/TCNQ membrane, which had a relatively high proportion of polyamide, showed a higher permeance without difference in selectivity. These unexpected data were attributable to the fact that the relatively abundant amount of PA groups in PEBAX-5513 was able to stabilize and positively polarize the surface of AgNPs, resulting in the stabilized and high performance of olefin separation.

Small molecule diffusion in poly-(olygo ethylene glycol methacrylate) based hydrogels studied by fluorescence correlation spectroscopy

Understanding just how solutes such as small molecules, polymers or proteins diffuse in “smart” hydrogels is a key factor in developing potential applications. In this work, we used fluorescence correlation spectroscopy (FCS) to study how structural parameters (length of side groups, network density) influence the diffusion of small dye molecules in poly (oligo (ethylene glycol) methyl ether methacrylates) (POEGMAs) hydrogels. Two diffusion components were found and attributed to (i) Fickian-like diffusion slowed only by steric effects, and (ii) diffusion slowed by interactions with the polymer. The relationship between the diffusion component (i) and the polymer concentration showed two regimes with different slopes in both hydrogels and solutions of non-crosslinked polymers, additionally studied for reference. The threshold between these regimes depended on the polymer hydrophilicity/hydrophobicity and the presence of cross-links. The release time of the model drug (ibuprofen) proved to be shorter in the case of denser hydrogel networks than for looser ones. This means that the drug affinity to the polymer network is the crucial parameter determining release processes, while the diffusion factor is of secondary and minor importance.

Local Structures and Dynamics of Imidazole Molecules in Poly(vinylphosphonic acid)–Imidazole Composite Investigated by Molecular Dynamics

The composite materials of acidic polymers and imidazole (Im) exhibit good high-proton conduction, making them potentially useful in proton-exchange membrane fuel cells. The proton conduction mechanism must be clearly elucidated for the design of future high proton-conduction materials. This study examines the local hydrogen-bonding structures and dynamics of Im for proton-conducting poly(vinylphosphonic acid)-Im (PVPA-xIm) composites by using molecular dynamics simulations. Radial distribution functions (RDFs) characterize the hydrogen bonds between Im or imidazolium cation (ImH+) and phosphonic acid (PA) group and among Im molecules. RDFs and diffusion coefficients suggest that the intercalation of Im to PVPA reduces Im mobility because of the interaction between Im and PA groups. However, similar to pure Im, the amount of Im with fast rotational motions increases as the amount of Im increases. Our study leads us to conclude that long-range proton transport occurs through the hydrogen-bonding network of...

Polyethyleneimine-polyethylene glycol copolymer targeted by anti-HER2 nanobody for specific delivery of transcriptionally targeted tBid containing construct

The present research seeks to investigate the process of mixing targeted gene delivery and transcriptional targeting. We have conjugated Polyethylenimine polymers (PEI) and molecules of poly (ethylene glycol). The next step was covalent attachment of anti-HER2 variables domains of camelid heavy chains antibodies (VHHs) or nanobodies (Nbs) to the distal terminals of NHS-PEG3500 in PEI-PEG nanoparticles. The whole procedure yielded PEI-PEG-Nb immunoconjugates. Having determined the properties of polyplexes, steps were taken to investigate the most efficient ratio of PEI polymers to pDNA molecules (N/P) so that the greatest rate of transfection may be obtained. This immune targeted nano biopolymer could condense the gene constructs that coded a transcriptionally targeted truncated –Bid (tBid) killer gene which was controlled by the breast cancer-specific MUC1 promoter. The favourable physicochemical properties matching both the size and zeta potential were observed in engineered polyplexes. Elevated transfection efficiency in HER2 positive cell lines using Nb-modified polyplexes were shown by the results of flow cytometry as compared against non-modified particles. 1.6 and 4.8 fold higher transfection efficiencies were observed in in vitro gene expression researches which used PEI-PEG-Nb/pGL4.50 compared to the situation when native PEI polymers were utilized in both BT-474 and SK-BR-3, respectively. A 2.22 and 3.62 fold rise in the level of tBid gene expression in BT-474 and SK-BR-3 cell lines relative to unmodified PEI treated cells was the result of transfection with PEI-PEG-Nb/pMUC1-tBid, respectively. In those HER2-positive cells which were transfected by targeted polyplexes, higher levels of cell death were observed. This fact points not only to the effective targeted delivery, but it is also indicative of transcriptional targeting efficiency of tBid killer gene when its expression is controlled by MUC1 promoter.

Flow Cytometry Study of the Non-Fickean Diffusion of Small-Charged Molecules in Poly(diallyl dimethyl ammonium chloride)/Poly(styrene sodium sulfonate) Multilayers: Impact of the Layer Number, Top Layer, and Concentration of Diffusing Molecules.

The diffusion of sodium dithionite (S2O42-) through polyelectrolyte multilayers of poly(diallyl dimethyl ammonium chloride) (PDADMAC)/poly(styrene sodium sulfonate) (PSS) assembled on colloidal particles with the layer-by-layer technique is studied by means of flow cytometry and quenching assay. Fluorescence is provided by a layer of (7-nitrobenz-2-oxa-1,3-diazol-4yl) amino) hexanoate (NBD)-labeled poly(allyl amine hydrochloride) assembled below the PDADMAC/PSS multilayer. NBD is quenched by a redox reaction with S2O42-. NBD quenching is fast at short times but strongly retarded at longer times. Quenching is faster for PDADMAC as the top layer and for increasing concentrations of S2O42-. The quenching kinetics of NBD is described with a model assuming a non-Fickean diffusion of S2O42-, with diffusion coefficients that depend on time with an inverse power law. Diffusion coefficients show little dependence on the number of layers but are highly dependent on the concentration of S2O42-. Increasing the concentration of S2O42- over 10 mol/m3 results in a decrease of the diffusion coefficient, more evident at longer times. The non-Fickean behavior for S2O42- diffusion is explained on the basis of the trapping of dithionites in the multilayers.

Dipole orientation polarization property of single-molecule manipulated by external electric field

The dipole orientation of single-molecule plays an important role in improving the fluorescence collection efficiency and promises to have applications in super-resolution imaging, protein folding, and Förster resonance energy transfer between fluorophores. However, these applications are realized usually by precisely manipulating the orientation of the dipole moment of single molecules. Here, the dipole orientation of 1,1′-dioctadecyl-3,3,3′,3′,-tetramethylindodicarbocyanine (DiD) single molecules with the permanent dipole moment of 14.9 D is manipulated by using an external electric field of 3500 V/mm. Single DiD molecules are prepared by using mixed solvent of chloroform and dimethyl sulfoxide. The dipole orientation of single molecules is manipulated by an external electric field during the evaporation of solvent. The fluorescence of single molecules is measured by splitting the fluorescence collected by an objective into the S-polarized and P-polarized beams, and the fluorescence polarization of single molecules can be calculated by measuring the intensities of two orthogonal channels (<i>I</i><sub>S</sub> and <i>I</i><sub>P</sub>). The distribution of dipole orientation angle (<i>α</i>) for single DiD molecules in poly-(methyl methacrylate) (PMMA) film is analyzed statistically, and its changes are compared under different electric fields. It is found that the dipole orientation angle <i>α</i> of single DiD molecules in the PMMA film without applying electric field obeys a single-peak Gaussian distribution with the most probable value of 41°, which results from the fluorescence dichroism signal of the high numerical aperture objective. Applying a perpendicular electric field to the surface of single-molecule sample, the distribution of dipole orientation angle <i>α</i> of single DiD molecules can be still fitted by a single-peak Gaussian function with the most probable value of 44.2°. The dipole orientation of single DiD molecules under the perpendicular electric field changes little. However, by applying a parallel electric field to the surface of single-molecule sample, the dipole orientation angle <i>α</i> of single DiD molecules changes prominently. It obeys a two-peak Gaussian distribution with the most probable values of ～ 32° and 55.5°, indicating that the orientation polarization of the dipole moment occurs to the single DiD molecules in PMMA film. The dipole orientation of single polar molecules tends to the parallel electric field in this case.

Doping mechanism in organic devices: Effects of oxygen molecules in poly(3-hexylthiophene) thin films

Abstract The electrical properties of poly(3-hexylthiophene) (P3HT) are very sensitive to the presence of oxygen, as well as in contact with several metals and oxides that are used as electrodes in organic devices. Such atoms and molecules have deleterious impact on the devices performance, normally causing the diminishing of their efficiency and operation lifetime. Therefore, understanding how those molecules, especially the oxygen, interact with the active layer is mandatory to prevent device degradation. Here we performed CELIV and dark Time-of-Flight measurements in a simplified diode structure ITO/P3HT/Ag before and after exposing the device to ambient air. The results analysis give evidence of a slow intake of oxygen molecules by diffusion, a deliberate filling of the generated oxygen traps by electrons and, consequently, a shift of the P3HT Fermi level toward the HOMO of P3HT. Finally the dynamics of hole extraction during CELIV measurements and their recovery are also discussed.

Biofunctionalisation of magnesium alloys by successive immobilisation of poly(ethylene glycol), fibronectin and heparin

In the present study, with the aim of improving their corrosion resistance, anticoagulation and cytocompatibility with endothelial cells, a magnesium alloy (AZ31B) was modified by the alkali heat treatment followed by the immobilisation of the dopamine layer. Subsequently, molecules of poly(ethylene glycol) (PEG) and fibronectin or fibronectin–heparin complexes were successively immobilised on the dopamine-modified surface. After the surface modification, the hydrophilicity of magnesium alloy was obviously improved. The corrosion resistance of the magnesium alloy was improved through alkali heat treatment, and the immobilisation of dopamine and PEG can further reduce the corrosion rate. However, the corrosion resistance of the magnesium alloy was slightly reduced by the grafting of fibronectin or fibronectin–heparin complex. Furthermore, the modified samples showed improved hemocompatibility and good cytocompatibility with the endothelial cells on the fibronectin or fibronectin–heparin-modified surfaces. Therefore, the corrosion resistance, anticoagulation and cytocompatibility of the magnesium alloy can be enhanced by alkali heat treatment and subsequent immobilisation of biomolecules. The method of this study can be used for surface modification of magnesium alloys to impart these with better corrosion resistance, blood compatibility and cytocompatibility with endothelial cells simultaneously.

Molecular and condition parameters dependent diffusion coefficient of water in poly(vinyl alcohol): a molecular dynamics simulation study

Diffusion behavior of water molecules in poly(vinyl alcohol) (PVA) was investigated by molecular dynamics (MD) simulation, and the diffusion coefficient of water molecules in PVA was calculated based on the Einstein’s relation. The effects of polymerization degree, temperature, density, and pressure on the diffusion coefficient were conducted to gain insights into their diffusion mechanisms under different processing conditions. The results showed that the simulation data of diffusion coefficient was consistent with experimental values. With the increase of polymerization degree of PVA, the diffusion coefficient began with a sharp decrease and then became stable, while the diffusion coefficient increased with increasing temperature. It was also found that PVA matrix with a smaller cell density had a larger free volume, and then, the diffusion coefficient was larger. The H2O sorption isotherm could be described by the Langmuir sorption isotherm, and the diffusion coefficient decreased with the increase of pressure.

Multichromophoric organic molecules encapsulated in polymer nanoparticles for artificial light harvesting.

We designed a self-assembled multichromophoric organic molecular arrangement inside polymer nanoparticles for light-harvesting antenna materials. The self-assembled molecular arrangement of quaterthiophene molecules was found to be an efficient light-absorbing antenna material, followed by energy transfer to Nile red (NR) dye molecules, which was confined in polymer nanoparticles. The efficiency of the antenna effect was found to be 3.2 and the effective molar extinction coefficient of acceptor dye molecules was found to be enhanced, which indicates an efficient light-harvesting system. Based on this energy-transfer process, tunable photo emission and white light emission has been generated with 14 % quantum yield. Such self-assembled oligothiophene-NR systems encapsulated in polymer nanoparticles may open up new possibilities for fabrication of artificial light harvesting system.

The Cluster Size and Change of Water Molecules in Poly(vinyl alcohol) Film by Heating

The Cluster Size and Change of Water Molecules in Poly(vinyl alcohol) Film by Heating

Low-pressure plasma enhanced immobilization of chitosan on low-density polyethylene for bio-medical applications

With the aim of improving blood compatibility of low density polyethylene (LDPE) films, an effective low-pressure plasma technology was employed to functionalize the LDPE film surfaces through in-situ grafting of acrylic acid (AAc). Subsequently, the molecules of poly(ethylene glycol) (PEG) and chitosan (CHI) were immobilized on the surface of grafted LDPE films. The unmodified and modified LDPE films were analyzed using various characterization techniques such as contact angle, atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and X-ray photo electron spectroscopy (XPS) to understand the changes in surface properties such as hydrophilicity, surface topography and chemical composition, respectively. Furthermore, LDPE films have been subjected to an ageing process to determine the durability of the plasma assisted surface modification. The blood compatibility of the surface modified LDPE films was confirmed by in vitro tests. It was found that surface modified LDPE films show better hydrophilic behavior compared with the unmodified one. FTIR and XPS results confirm the successful immobilization of CHI on the surface of LDPE films. LDPE films showed marked morphological changes after grafting of AAc, PEG and CHI which were confirmed through AFM imaging. The in vitro blood compatibility tests have clearly demonstrated that CHI immobilized LDPE films exhibit remarkable anti thrombogenic nature compared with other modified films. Surface modified LDPE films through low-pressure plasma technique could be adequate for biomedical implants such as artificial skin substrates, urethral catheters or cardiac stents, among others.

Stretching of DNA confined in nanochannels with charged walls.

There is currently a growing interest in control of stretching of DNA inside nanoconfined regions due to the possibility to analyze and manipulate single biomolecules for applications such as DNA mapping and barcoding, which are based on stretching the DNA in a linear fashion. In the present work, we couple Finite Element Methods and Monte Carlo simulations in order to study the conformation of DNA molecules confined in nanofluidic channels with neutral and charged walls. We find that the electrostatic forces become more and more important when lowering the ionic strength of the solution. The influence of the nanochannel cross section geometry is also studied by evaluating the DNA elongation in square, rectangular, and triangular channels. We demonstrate that coupling electrostatically interacting walls with a triangular geometry is an efficient way to stretch DNA molecules at the scale of hundreds of nanometers. The paper reports experimental observations of λ-DNA molecules in poly(dimethylsiloxane) nanochannels filled with solutions of different ionic strength. The results are in good agreement with the theoretical predictions, confirming the crucial role of the electrostatic repulsion of the constraining walls on the molecule stretching.

Structural characterization of new defective molecules in poly(amidoamide) dendrimers by combining mass spectrometry and nuclear magnetic resonance

A new side-reaction occurring during divergent synthesis of PAMAM dendrimers (generations G0–G2) was revealed by mass spectrometric detection of defective molecules with a net gain of a single carbon atom as compared to expected compounds. Combining MS/MS experiments performed on different electrosprayed precursor ions (protonated molecules and lithiated adducts) with NMR analyses allowed the origin of these by-products to be elucidated. Modification of one ethylenediamine end-group of perfect dendrimers into a cyclic imidazolidine moiety was induced by formaldehyde present at trace level in the methanol solvent used as the synthesis medium. Dendrimers studied here were purposely constructed from a triethanolamine core to make them more flexible, as compared to NH3- or ethylenediamine-core PAMAM, and hence improve their interaction with DNA. Occurrence of this side-reaction would be favored by the particular flexibility of the dendrimer branches.

Electric field induced fluorescence hysteresis of single molecules in poly(methyl methacrylate)

Single molecule (SM) chips could serve as the fundamental devices in quantum information processing. In this context, a chip with the non-polar SMs of squaraine-derived rotaxanes embedded in a polar poly(methyl methacrylate) matrix was realized and the SM fluorescence hysteresis induced by the electric field was observed at room temperature. Here, we presented a model considering both of the electron transfer and space charge relaxation processes to explain the fluorescence hysteresis effect, and the model-based simulations agreed reasonably well with the experimental results.

Messenger RNas : their utilization and degradation during pollen germination and tube growth

During pollen germination and tube growth at least 230 new proteins are synthesized, as determined by <sup>35</sup>S-methionime labeling and two dimensional gel electrophoretic analysis of the labeled proteins. The same number and pattern of protein spots is seen whether or not actinomycin D is included in the, medium, indicating that the mRNAs present in the unger-minated pollen grain and those newly synthesized code for the same proteins. The genetic program during at least the latter part of pollen maturation prior to anthesis and that during pollen germination and tube growth thus appears to be similar if not identical. During the first hour of pollen tube growth about 500/0 of the protein synthesis that occurs utilizes previously synthesized mRNAs. The remaining 50% occurs on newly made mRNAs. The ungerminated mature pollen grain contains 196 pg of RNA and approximately 6 X 10<sup>6</sup> molecules of poly(A)+ RNA, i.e. mRNAs. The rate of protein synthesis corrected for internal pool changes in the labeled amino acid used (<sup>3</sup>H-leucine) is highest during the first 15 min of pollen tube growth. The rate decreases rapidly thereafter for the next 45 min. Concurrent with the reduction in rate of protein synthesis there is a reduction in the poly(A) content of the pollen RNA and in the amount of poly(A) per pollen, grain. The total RNA per pollen grain, however, appears not to change during this period.

Combinatorial co-encapsulation of hydrophobic molecules in poly(lactide-co-glycolide) microparticles

There is great interest for developing poly(lactide-co-glycolide) (PLGA) based particles for targeted delivery and controlled release of encapsulated biological molecules. These PLGA particles can be used to deliver proteins, small molecule drugs and nucleotides. Furthermore, it has been shown that the co-encapsulation of multiple factors in PLGA particles can generate synergistic responses, and can also provide theranostic capability. However, the number of possible unique particle formulations that may be generated by the combination of different components in a particle increases dramatically with each new component, and currently, there is no method to generate large libraries of unique PLGA particles. In order to address this gap, we have developed a high-throughput methodology to produce hundreds of small batches of particles. The particles are generated in multi-well plate wells by a modified oil-in-water emulsion technique. In order to demonstrate the versatility of this technique, combinatorial formulations of six different loading concentrations of three fluorescent dyes were fabricated giving rise to 216 unique PLGA particle formulations. We demonstrate systematic and well-controlled combinatorial loading of hydrophobic molecules into the particles. This parallel particle production (PPP) methodology potentiates the generation of hundreds of different combinatorial particle formulations with multiple co-encapsulates in less than 24 h in standard polystyrene multi-well plates, thus providing rapid, low cost, high-throughput production. We envision that such a PPP library of particles encapsulating combinations of drugs and imaging modalities can subsequently be tested on small populations of cells in a high-throughput fashion, and represents a step toward personalized medicine.

Roles of the PI3K/Akt pathway and autophagy in TLR3 signaling-induced apoptosis and growth arrest of human prostate cancer cells.

Toll-like receptors (TLRs) are widely expressed in immune cells and play a crucial role in many aspects of the immune response. Although some types of TLRs are also expressed in cancer cells, the effects and mechanisms of TLR signaling in cancer cells have not yet been fully elucidated. In the present study, we analyzed the effects of polyinosinic-polycytidylic acid [poly(I:C)], a TLR3 ligand, on three TLR3-expressing human prostate cancer cell lines (LNCaP, PC3, and DU145). We then further characterized the underlying mechanisms, focusing on the poly(I:C)-sensitive LNCaP cell line. Poly(I:C) significantly reduced the viability of LNCaP cells TLR3 and endosome dependently. One mechanism for the antitumor effect was caspase-dependent apoptosis, and another mechanism was poly(I:C)-induced growth arrest. Cell survival and proliferation of LNCaP cells depended on the PI3K/Akt pathway, and PI3K/Akt inhibitors induced apoptosis and growth arrest similar to poly(I:C) treatment. Additionally, poly(I:C) treatment caused dephosphorylation of Akt in LNCaP cells, but transduction of the constitutively active form of Akt rendered LNCaP cells resistant to poly(I:C). Immunoblot analysis of proliferation- and apoptosis-related molecules in poly(I:C)-treated LNCaP cells revealed participation of cyclinD1, c-Myc, p53, and NOXA. Interestingly, poly(I:C) treatment of LNCaP cells was accompanied by autophagy, which was cytoprotective toward poly(I:C)-induced apoptosis. Together, these findings indicate that TLR3 signaling triggers apoptosis and growth arrest of LNCaP cells partially through inactivation of the PI3K/Akt pathway and that treatment-associated autophagy plays a cytoprotective role.