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81.
Polymer therapeutics: concepts and applications 总被引:14,自引:0,他引:14
Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems. 相似文献
82.
本文通过聚乙二醇化的聚乙烯亚胺与马来酰化的壳聚糖反应,得到了水溶性良好的聚乙二醇化聚乙烯亚胺接枝的壳聚糖(CS-N-PEI-mPEG),目标物用FT-IR,1H-NMR,UV-Vis进行了表征。实验表明,CS-N-PEI-mPEG对细胞的毒性低,而它的转染效率却较高。 相似文献
83.
(ML0.70Mg0.12Zr0.07Gd0.05MY0.06)Ni2.87Al0.08Co0.15是具有快速充电能力的AB3型负极合金材料,将此负极合金与正极以及尼龙或聚丙烯隔膜组成的快充形MH-Ni电池,研究了负极合金与隔膜的相互匹配性。结果表明:用交联型聚丙烯酸盐对隔膜改性生成的聚丙烯隔膜与该AB3型负极合金有良好的匹配性。 相似文献
84.
Sonoporation, ultrasound-mediated membrane perforation can potentially puncture plasma membrane and rigid cell wall on presumably reversible basis which benefit gene transfection and plant biotechnology. Herein, positively charged poly-ethyleneimine (PEI)-coated mesoporous silica nanoparticles (MSNs) with an average diameter of 100 ± 8.7 nm was synthesized for GUS-encoding plasmid delivery into the suspended tobacco cells using the ultrasound treatment. The overall potential of PEI-MSN for DNA adsorption was measured at 43.43 μg DNA mg−1 PEI-MSNs. It was shown that high level of sonoporation may adversely upset the cell viability. Optimal conditions of ultrasonic treatment are obtained as 8 min at 3 various intensities of 160, 320 and 640 W. Histochemical staining assay was used to follow the protein expression. It was shown that PEI-coated MSNs efficiently transfer the GUS-encoding plasmid DNA into the tobacco cells. The results of this study showed that ultrasonic treatment provides an economical and straightforward approach for gene transferring into the plant cells without any need to complicated devices and concerns about safety issues. 相似文献
85.
The chemical structure of methylated poly(1‐vinylimidazole) (PVIm‐Me) has been tuned for gene carrier properties, which are cell viability, the stability of its DNA polyion complexes, and gene expression. The resulting PVIm‐Me with lower methylation degree (6 and 20 mol%) exhibited no significant cytotoxicity, as compared with 40 mol% PVIm‐Me, in spite of the same concentration and chemical structure of positive charges. The DNA complex with 20 mol% PVIm‐Me stably retained the DNA, as compared with 6 or 40 mol% PVIm‐Me, which was examined by competitive exchange with dextran sulfate. As a result, the DNA complex with 20 mol% PVIm‐Me mediated most efficient gene delivery, where the resulting transfection activity was higher than that mediated by a positive control, poly(ethylenimine). These results suggest that the optimization of the balance of the methylimidazolium and the imidazole groups of PVIm‐Me is essential for gene carrier design. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
86.
A Tailor‐Made Specific Anion‐Binding Motif in the Side Chain Transforms a Tetrapeptide into an Efficient Vector for Gene Delivery
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Mao Li Stefanie Schlesiger Prof. Shirley K. Knauer Prof. Carsten Schmuck 《Angewandte Chemie (International ed. in English)》2015,54(10):2941-2944
Arginine‐rich cell‐penetrating peptides are widely utilized as vectors for gene delivery. However, their transfection efficacy still needs to be optimized. To accomplish this, guanidinocarbonylpyrrole groups, which are tailor‐made anion binding sites, were introduced into the side chains of tetralysine to obtain the peptide analogue 1 . In contrast to the common strategy of adding a lipophilic tail to peptide vectors, this novel method most likely enhances transfection efficacy through more specific interactions between the binding motifs and DNA or the cell membrane. Tetrapeptide analogue 1 is thus the smallest peptidic transfection vector that has been reported to date. The transfection efficacy of 1 , which on average has less than two positive charges under physiological conditions, is even better than that of polyethylenimine (PEI). Furthermore, 1 exhibits only negligible cytotoxicity, which makes it an interesting candidate for further development. 相似文献
87.
J Li Y Zhu ST Hazeldine C Li D Oupický 《Angewandte Chemie (International ed. in English)》2012,51(35):8740-8743
Giving a one-two punch: A bicyclam-based biodegradable polycation with CXCR4 antagonistic activity shows potential for combining cancer chemotherapy with gene therapy or siRNA therapy. This dual-function polycation prevents cancer cell invasion by inhibiting CXCL12-stimulated CXCR4 activation, while at the same time efficiently and safely delivering therapeutic DNA into cancer cells. 相似文献
88.
A cDNA clone, p14--6, which has an antioncogene activity on the v--Ki--Ras oncogene-transformed malignant cell line DT, was found. This clone was recovered from the revertantR14 cells, which had been isolated by transfections of DT cells with a normal human fibro-blast cDNA library cloned in pcD2, an Okayama-Berg vector. When transfected into DT cells,p14--6 clone gave rise to phenotypical flat reversion in 5--15% of DT transfectant colo-nies. The p14--6--transfected flat cell line, RR, was proven to be a true revertant with signif-icantly reduced malignancy by in ritro and in riro malignancy tests. All other clones recov-ered from R14 cells were unable to cause this reversion. Molecular hybridizations showedthat the p14--6 was inserted into RR genome as tandem repeats, and no structural changewas found in the D--Ki--Ras oncogene in RR genome. These facts suggest that the antioncogeneactivity of the p14--6 clone on the DT cells may be exerted through expression of thecDNA contained in this clone. Possib 相似文献
89.
Five novel cationic lipids with fully or partiallynon-scissile linkage regions between the pseudoglyceryl backbone and the hydrocarbon chains have been synthesized. The membrane-forming
properties of these new lipids are briefly presented. 相似文献
90.
超分子聚合物通常以非共价键作为构筑驱动力,其结构具有动态可逆的特点,在新型响应性聚合物材料中具有突出优势。环糊精可通过主客体识别作用与客体分子如二茂铁、偶氮苯、金刚烷、苯环等形成包合,以此构筑的超分子组装体展现出丰富的自组装-解组装特性、刺激响应性、较低的细胞毒性和较好的生物相容性,有望在药物/基因载体领域得到应用。本文从环糊精超分子聚合物的生物医用出发,着重对近年来环糊精超分子聚合物载体在药物控制释放、基因转染以及药物/基因共递送三方面的研究进展进行了总结和评述,并在此基础上展望了环糊精超分子聚合物的研究方向和发展趋势。 相似文献