Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0276640 (TEM)
 20,729 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Signal-mediated nuclear transport is a gated process that occurs through a central transporter element located within the pore complex. The purpose of this investigation was to identify the region of the transporter that functions as the gate; i.e. the region that restricts passive diffusion of macromolecules through the pores. To accomplish this, small gold particles coated with polyethylene glycol (PEG; total particle diameter 40-70 A) or large PEG-particles (total diameter 110-270 A) were microinjected into the cytoplasm or nucleoplasm of Xenopus oocytes. Since PEG does not contain either nuclear import or export signals, it is assumed that the particles distribute by simple diffusion. The cells were fixed after 5 or 30 minutes and subsequently examined using TEM. The distribution of the particles located adjacent to and within the pore complexes was then mapped. The results obtained at both 5 and 30 minutes after cytoplasmic injections of small gold were basically the same. The particles readily entered the transporter but, on the average, were approximately 11 times more concentrated in the cytoplasmic half of this structure. The opposite distribution was observed following nuclear injections, i.e. the particles that were located in the transporter were approximately 7 times more numerous in the nuclear half. Our data indicate that there is a single transport gate located in the central domain of the transporter that restricts passive diffusion. The large particles that were injected into the cytoplasm migrated to the surface of the pore complex, but entered the transporter less frequently than small gold. Interestingly, the diffusion of large PEG-particles to the surface of the pores following nuclear injection was greatly restricted; however, this was not the case for similar size particles that were coated with protein containing nuclear export signals (NES). The latter results suggest that the NES is not only required for translocation, but also for migration within the nucleoplasm.
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PMID:The location of the transport gate in the nuclear pore complex. 936 76

In this paper, a systematic study of the influence of various experimental parameters on the morphology and size of CaCO3 crystals after room-temperature crystallization from water in the presence of poly(ethylene glycol)-block-poly(methacrylic acid) (PEG-b-PMAA) is presented. The pH of the solution, the block copolymer concentration, and the ratio [polymer]/[CaCO3] turned out to be important parameters for the morphogenesis of CaCO3, whereas a moderate increase of the ionic strength (0.016 M) had no influence. Depending on the experimental conditions, the crystal morphologies can be tuned from calcite rhombohedra via rods, ellipsoids or dumbbells to spheres. A morphology map is presented which allows the prediction of the crystal morphology from a combination of pH, and CaCO3 and polymer concentration. Morphologies reported in literature for the same system but under different crystallization conditions agree well with the predictions from the morphology map. A closer examination of the growth of polycrystalline macroscopic CaCO3 spheres by TEM and time-resolved dynamic light scattering showed that CaCO3 macrocrystals are formed from strings of aggregated amorphous nanoparticles and then recrystallize as dumbbell-shaped or spherical calcite macrocrystal.
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PMID:A systematic examination of the morphogenesis of calcium carbonate in the presence of a double-hydrophilic block copolymer. 1120 2

A trifluoroethylester-terminal poly(ethylene glycol) (PEG) silane was synthesized and self-assembled on iron oxide nanoparticles. The nanoparticle system thus prepared has the flexibility to conjugate with cell targeting agents via either carboxylic or amine terminal groups for a number of biomedical applications, including magnetic resonance imaging (MRI) and controlled drug delivery. The trifluoroethylester silane was synthesized by modifying a PEG diacid to form the corresponding bistrifluoroethylester (TFEE), followed by a reaction with 3-aminopropyltriethoxysilane (APS). The APS coupled with PEG chains confers the stability of PEG self-assembled monolayers (SAMs) and increases the PEG packing density on nanoparticles by establishing hydrogen bonding between the carbonyl and amine groups present within the monolayer structure. The success of the synthesis of the PEG TEFE silane was confirmed with (1)H NMR and Fourier transform infrared spectroscopy (FTIR). The conjugating flexibility of the PEG TEFE was demonstrated with folic acid that had carboxylic acid groups and amine terminal groups, respectively, and was confirmed by FTIR. TEM analysis showed the well-dispersed nanoparticles before and after they were coated with PEG and folic acid.
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PMID:A bifunctional poly(ethylene glycol) silane immobilized on metallic oxide-based nanoparticles for conjugation with cell targeting agents. 1518 57

Several samples of polymeric micelles, formed by amphiphilic derivatives of PHEA, obtained by grafting into polymeric backbone of PEGs and/or hexadecylamine groups (PHEA-PEG-C(16) and PHEA-C(16)) and containing different amount of Tamoxifen, were prepared. All Tamoxifen-loaded polymeric micelles showed to increase drug water solubility. TEM studies provided evidence of the formation of supramolecular core/shell architectures containing drug, in the nanoscopic range and with spherical shape. Samples with different amount of encapsulated Tamoxifen were subjected to in vitro cytotoxic studies in order to evaluate the effect of Tamoxifen micellization on cell growth inhibition. All samples of Tamoxifen-loaded polymeric micelles showed a significantly higher antiproliferative activity in comparison with free drug, probably attributable to fluidification of cellular membranes, caused by amphiphilic copolymers, that allows a higher penetration of the drug into tumoral cells. To gain preliminary information about the potential use of prepared micelles as Tamoxifen drug delivery systems, studies evaluating drug release ability of micelle systems in media mimicking biological fluids (buffer solutions at pH 7.4 and 5.5) and in human plasma were carried out. These studies, performed evaluating the amount of Tamoxifen that remains in solution as a function of time, showed that at pH 7.4, as well as in plasma, PHEA-C(16) polymeric micelles were able to release lower drug amounts than PHEA-PEG(5000)-C(16) ones, while at pH 5.5, the behavior difference between two kind of micelles was less pronounced.
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PMID:Tamoxifen-loaded polymeric micelles: preparation, physico-chemical characterization and in vitro evaluation studies. 1552 97

Nanoparticles have been widely used for a variety of biomedical applications and there is a growing need for highly specific and efficient uptake of the nanoparticles into target cells. Poly(ethylene glycol) (PEG), folic acid (FA), and their conjugate PEG-FA were attached to magnetite nanoparticles to compare their effects on the improvement of intracellular uptake of the nanoparticles to human breast cancer cells, BT-20. AFM and TEM results indicated that the nanoparticles after surface modification were monodisperse, with coatings on individual nanoparticles. The cell culture experiments showed that the PEG-FA coated nanoparticles were internalized into BT-20 cancer cells and exhibited higher efficiency of intracellular uptake than only PEG- or FA-coated nanoparticles. The surface modification protocols can also be used to modify the surfaces of other nanoparticles for targeting intracellular delivery.
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PMID:Surface modification of monodisperse magnetite nanoparticles for improved intracellular uptake to breast cancer cells. 1572 4

AAV gene therapy vectors have significant clinical promise, but serum neutralization poses a challenge that must be overcome. We have examined the potential of conjugating the AAV surface with activated polyethylene glycol chains to protect the vector from neutralizing antibodies. Two key parameters were investigated: the polymer chain size and the PEG:lysine conjugation ratio. Transduction data revealed that the vector is fully infectious until a critical PEG conjugation reaction ratio was exceeded, and this critical level was found to vary with polymer chain size. At this key conjugation ratio, however, particles were moderately protected from serum neutralization, 2.3-fold over unmodified vector, demonstrating that there is a small window of PEGylation for which particles are still fully infective and benefit from antibody protection. TEM results and structural analysis indicate that the drop of infectivity as the PEG concentration is increased beyond the critical conjugation ratio may be due to a combination of steric interference with viral regions necessary for infection as well as reaction at important lysine residues. However, this first study analyzing the potential of PEG to protect AAV from serum neutralization shows that the approach has promise, which can be further enhanced if the locations of PEG attachment can be more finely controlled.
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PMID:PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization. 1593 53

The purpose of this work was to investigate the physical properties of drug-loaded poly(methacrylic acid-g-ethylene glycol) {P(MAA-g-EG)} particles, their biocompatibility with the gastrointestinal tract of rats and also the effects of these particles on the tight junctions of the rat intestinal epithelium. Model drugs such as diltiazem HCl, diclofenac Na, ciprofloxacin HCl and isoniazid were used in this study. P(MAA-g-EG) particles were prepared by free radical solution polymerization of methacrylic acid (MAA) and poly(ethylene glycol) (PEG). The loading efficiency of the model drugs in the particles and in vitro release profiles were investigated in pH 7.4 phosphate buffer and in gradually pH changing buffers (pH 1.2, 5.8, 6.8 and 7.4). The stability of free particles and drug-loaded particles was established by Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). In conclusion, P(MAA-g-EG) particles controlled the release rate of small molecular weight model drugs according to the pH of the medium. Stability of those particles loaded with drugs did not change in accelerated stability conditions. Histopathological results indicated that loading drugs to the particles prevented cell and tissue damage after 20 h. Free particles showed no change of tight junctions after 2 and 10 h. The results of TEM showed that increasing the amount of P(MAA-g-EG) particles from 100 to 385 mg clearly opened the tight junction, but with serious epithelial cell disruption.
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PMID:Release behaviour and biocompatibility of drug-loaded pH sensitive particles. 1642 23

In order to improve the absorption of nanoparticles in the brain following nasal administration, a novel protocol to conjugate biorecognitive ligands-lectins to the surface of poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles was established in the study. Wheat germ agglutinin (WGA), specifically binding to N-acetyl-D-glucosamine and sialic acid, both of which were abundantly observed in the nasal cavity, was selected as a model lectin. The WGA-conjugated nanoparticles were prepared by incorporating maleimide in the PLA-PEG molecular and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothialane thiolated WGA. Coupling of WGA with the PEG-PLA nanoparticles was confirmed by the existence of gold-labeled WGA-NP under TEM. The retention of biorecognitive activity of WGA after the covalent coupling procedure was confirmed by haemagglutination test. The resulting nanoparticles presented negligible nasal ciliatoxicity and the brain uptake of a fluorescent marker-coumarin carried by WGA functionized nanoparticles was about 2 folds in different brain tissues compared with that of coumarin incorporated in the unmodified ones. Thus, the technique offered a novel effective noninvasive system for brain drug delivery, especially for brain protein and gene delivery.
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PMID:Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration. 1651 Jan 78

The phase behavior of poly(ethylene glycol) grafted liposomes (PEG-liposomes) was investigated by differential scanning calorimetry (DSC), dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM). PEG-liposomes were prepared from mixtures of dipalmitoyl phosphatidylcholine (DPPC) and distearoyl phosphatidylethanolamine with a covalently attached PEG molecular weight of 2000 (DSPE-PEG2000). From the results of DLS measurements, the coexistence of PEG-liposomes and small molecular assemblies were confirmed at mole fractions of DSPE-PEG2000 above about 0.1. Moreover, it was confirmed that small molecular assemblies were disk micelles by cryo-TEM. However, the phase transition enthalpies of PEG-liposomes were hardly changed according to the DSC measurement, though the mole fraction of the PEG lipid increased. From these results, it was suggested that the phase transition enthalpies hardly changed despite mixed micelles being formed because the bilayer structure of the disk micelle maintains high cooperativity between the DPPC molecules.
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PMID:Calorimetry and cryo-transmission electron microscopic studies of PEG2000-grafted liposomes. 1659 66

Here we describe a very efficient method to produce well-defined amphiphilic gold nanoparticles (Au NPs) with an equal number of hydrophobic and hydrophilic arms which are distributed along the surface of a 2-nm gold core in an alternating fashion. The strategy involves direct coupling of V-shaped block copolymer amphiphile 2 with a carboxylic group at its junction point to mercaptophenol-terminated Au NPs. The reaction proceeds under mild esterification conditions and yields the product with a molecular weight of 40 kDa, high grafting density (2.9 chains/nm2), and extremely low polydispersity (1.07). The big advantage of this approach is the opportunity to avoid the use of expensive and often inaccessible polymeric thiols. The method described here is applicable to any carboxyl-terminated molecules and can be used for the preparation of complex, yet well-defined, macromolecular hybrid structures such as 1 (Au(PB-PEG)n). The new product, which was characterized by a combination of SEC, NMR, UV-vis, DLS, and TEM, represents a unique example of gold nanoparticles soluble in any conventional solvent.
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PMID:Amphiphilic gold nanoparticles with V-shaped arms. 1660 22


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