No abstract

Glioblastoma is a fatal primary malignant brain tumor, and the 5-year survival rate of treated glioblastoma patients still remains <5%. Considering the sustained development of metastasis, tumor recurrence, and drug resistance, there is an urgent need for the novel therapeutic approaches to combat glioblastoma. Trivalent arsenic derivative (arsenite, AsIII) with remarkable clinical efficacy in leukemia has been shown to exert cytocidal effect against glioblastoma cells. Gamabufotalin, an active bufadienolide compound, also shows selective cytocidal effect against glioblastoma cells, and has been suggested to serve as a promising adjuvant therapeutic agent to potentiate therapeutic effect of conventional anticancer drugs. In order to gain novel insight into therapeutic approaches against glioblastoma, the cytotoxicity of AsIII and gamabufotalin was explored in the human glioblastoma cell lines U-87 and U-251. In comparison with U-251 cells, U-87 cells were highly susceptible to the two drugs, alone or in combination. More importantly, clinically achieved concentrations of AsIII combined with gamabufotalin exhibited synergistic cytotoxicity against U-87 cells, whereas showed much less cytotoxicity to human normal peripheral blood mononuclear cells. G2/M cell cycle arrest was induced by each single drug, and further augmented by their combination in U-87 cells. Downregulation of the expression levels of cdc25C, Cyclin B1, cdc2, and survivin was observed in U-87 cells treated with the combined regimen and occurred in parallel with G2/M arrest. Concomitantly, lactate dehydrogenase leakage was also observed. Intriguingly, SB203580, a specific inhibitor of p38 MAPK, intensified the cytotoxicity of the combined regimen in U-87 cells, whereas wortmannin, a potent autophagy inhibitor, significantly rescued the cells. Collectively, G2/M arrest, necrosis and autophagy appeared to cooperatively contribute to the synergistic cytotoxicity of AsIII and gamabufotalin. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a possible strategy composed of AsIII, gamabufotalin, and a p38 MAPK inhibitor may provide novel insight into approaches designed to combat glioblastoma.

We describe a biodegradable amphiphilic polyurethane (PU) with disulfide bonds in the main chain [PEtOz- b -PU(SS)- b -PEtOz]. This multi-block PU was synthesized using poly (ε-caprolactone) diol (PCL-SS-PCL) and poly (2-ethyl-2-oxazoline) (PEtOz-OH) as soft segments, and bis (2-isocyanatoethyl) disulfide as the hard segment. Acid-sensitive PEtOz-OH was used as a hydrophilic segment for pH sensitivity. And reduction sensitivity was induced via disulfide bonds incorporated into the hydrophobic poly (ε-caprolactone) segment of the amphiphilic PUs. The system can self-assemble to form micelles responsive to pH and reducing conditions. The properties of the micelle were studied with dynamic light scattering and scanning electron microscopy. Doxorubicin (DOX) was chosen as a model drug. The in vitro release studies showed that PEtOz- b -PU(SS)- b -PEtOz micelle could degrade more rapidly and completely in a reductive and acidic environment [10 mM dl -Dithiothreitol, pH 5.0]. The methyl tetrazolium (MTT) assay and fluorescent microscopy confirmed the cytotoxicity of the DOX-loaded micelles. This work provides a promising dual-responsive drug carrier based on amphiphilic PU to achieve efficient drug delivery.

A series of disulfide-linked amphiphilic polymers polyoxaline-SS-poly(lactide) (PEtOx-SS-PLA) were prepared and self-assembled into nano-micelles in water.

We report a general strategy for functionalizing the sidewalls of carbon nanotubes (CNTs), which is based on electrophilic substitution reactions on phenylated CNTs. By using this strategy, four new functionalized CNTs were prepared, including diphenyl ketone, benzenesulfonyl chloride, benzyl chloride and thiophenol modified CNTs. The benzenesulfonyl chloride and benzyl chloride functinalized CNTs could serve as novel initiators for surface-initiated atom transfer radical polymerization. The thiophenol modified CNTs were used in immobilizing Pd nanoparticles on the CNT surface, and the CNT/Pd hybrid produced exhibits good catalytic efficiency for the electrochemical oxidation of methanol.

Polyurethanes (PUs) have various biomedical applications including controlled drug delivery. However, the incompletely release of drug at tumor sites limits the efficiency of these drug loaded polyurethane micelles. Here we report a novel polymer poly(2-ethyl-2-oxazoline)-SS-polyurethane-SS-poly(2-ethyl-2-oxazoline) triblock polyurethane (PEtOz-PU(PTMCSS)-PEtOz). The hydrophilic pH-responsive poly(2-ethyl-2-oxazoline) was used as an end-block to introduce pH responsiveness, and the hydrophobic PU middle-block was easily synthesized by the reaction of poly (trimethylene carbonate) diol containing disulfide bonds (PTMC-SS-PTMC diol) and bis (2-isocyanatoethyl) disulfide (CDI). PEtOz-PU(PTMCSS)-PEtOz could self-assemble to form micelles (176 nm). The drug release profile of PEtOz-PU(PTMCSS)-PEtOz micelles loaded with Doxorubicin (DOX) was studied in the presence of acetate buffer (10 mM, pH 5.0) and 10 mM dithiothreitol (DTT). The results showed that under this environment, DOX-loaded polyurethane micelles could release DOX faster and more thoroughly, about 97% of the DOX was released from the DOX-loaded PEtOz-PU(PTMCSS)-PEtOz micelle. In addition, fluorescent microscopy and cell viability assays validated that the DOX-loaded polyurethane micelle strongly inhibits the growth of C6 cells, suggesting their potential as a new nanomedicine against cancer.

No abstract

Copolymers of oligo(oxyethylene) methacrylates and a series of polar comonomers, i.e. acrylamide, acrylonitrile and maleic anhydride, were synthesized as media for dual‐ or single‐ion conduction, and correlation between polymer structure and properties was established through detailed studies on polymer morphology, mechanical property and the ion transport process. Polar groups in the polymer chain sequence were found to enhance matrix polarity and to retard oligoether crystallization, as well as to raise chain rigidity. Therefore, both novel dual‐ and single‐ion conduction are realized, with a simultaneous improvement in the mechanical properties of polymer materials. An investigation about the effect of matrix polarity on the ion transport process is also carried out, making use of the concepts concerning polymer segmental relaxation. Hence the enhanced matrix polarity is found to contribute to the improvement in ion conduction, mainly through its promotion of salt dissociation. However, at high temperature this facilitation is counteracted due to the “anomalous” temperature‐dependence of salt dissociation in the polymer matrix, and the higher the matrix polarity, the more drastic is the drop in carrier number with rising temperature.