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学科主题: 高分子化学
题名: The intracellular plasmid DNA localization of cationic reducible cholesterol-disulfide lipids
其他题名: 生物还原响应型胆固醇二硫脂质的细胞内定位行为
作者: Sheng RL(盛瑞隆) ; Luo T(罗挺) ; Zhu YD(朱英丹) ; Li H(李慧) ; Sun JJ(孙景景) ; Chen SD(陈圣典) ; Sun WY(孙文艳) ; Cao AM(曹阿民)
通讯作者: 曹阿民
刊名: Biomaterials
发表日期: 2011
卷: 32, 期:13, 页:3507-3519
收录类别: SCI
部门归属: 中科院上海有机化学研究所
英文摘要: Stimuli-responsive biomaterials derived from natural products toward efficient drug/gene delivery have been attracting increasing attention in the past decade. In this work, we first designed and prepared a new series of cholesterol-disulfide lipids, namely CHOSS-N, CHOSS-N+, CHOSS-Lys and CHOSS-4N bearing cholesterol and a variety of headgroups via disulfide and carbonate bond linkages, and their molecular structures were characterized by NMR and ESI-MS. Furthermore, plasmid DNA binding affinity for these new CHOSS lipids was separately examined by ethidium bromide displacement and agarose-gel retardant assay. Average diameter sizes and surface potentials of the CHOSS/pDNA lipoplex particles prepared under various N/P charge ratios were analyzed by dynamic laser light scattering (DLS). Under 10 mm dithiothreitol (DTT), stability and disassembly of the CHOSS/pDNA lipoplex nanoparticles were investigated by agarose-gel retardant assay and atomic force microscopy (AFM). Employing a COS-7 cell line, cell viability was examined for the prepared CHOSS lipids and their pDNA lipoplexes with branched PEI-25k as the reference. Finally, COS-7 cell gene transfection efficacies with these CHOSS lipids as potential delivery vectors were investigated by luciferase and EGFP transfection assay in the absence and presence of serum, and intracellular uptake capability, trafficking and cellular localization of Cy3-labeled pEGFP-N1 DNA were studied with a flow cytometer and fluorescent microscopy with Lipofectamine (TM) 2000 as the control. The results demonstrated low cytotoxicity, strong pDNA binding affinity and high transgenetic efficacy for new prepared CHOSS lipids, and particularly high intracellular uptake capability and specific cellular localization of pDNA at the periphery of cell nuclei were for the first time interestingly observed for the CHOSS lipid delivery carriers. In general, these may pave a new way to utilize cholesterol, amino acids and other functional natural products to prepare efficient gene/drug delivery carriers with simple structure and low cytotoxicity. (C) 2011 Elsevier Ltd. All rights reserved.
语种: 英语
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WOS记录号: WOS:000288884800017
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内容类型: 期刊论文
URI标识: http://ir.sioc.ac.cn/handle/331003/22964
Appears in Collections:高分子材料研究室_期刊论文

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Recommended Citation:
Sheng RL,Luo T,Zhu YD,et al. The intracellular plasmid DNA localization of cationic reducible cholesterol-disulfide lipids[J]. Biomaterials,2011,32(13):3507-3519.
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