"Intelligent" nanoassembly for gene delivery: in vitro transfection and the possible mechanism.

"Intelligent" nanoassembly for gene delivery: in vitro transfection and the possible mechanism.
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用于基因传递的“智能”纳米组装:体外转染和可能的机制。

DOI:
10.1016/j.ijpharm.2009.09.026
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发表时间:
2010
影响因子:
5.8
通讯作者:
Yaping Li
Yaping Li
中科院分区:
医学2区
文献类型:
--
作者:
Zhenghong Xu;Lingli Chen;Zhiwen Zhang;Wangwen Gu;Yaping Li

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设计并研究了一种新型的“智能”纳米组装体(INA),该纳米组装体由含有硫酸鱼精蛋白(PS)的pDNA浓缩核和含有聚乙二醇-二硫化物-涂料(PSD)的二油基磷脂酰乙醇胺(DOPE)脂质包膜组成。体外释放实验在含有10mM谷胱甘肽的溶液中进行,反映细胞内环境的氧化还原电位。实验结果表明,PSD具有良好的自去pegylation能力,可以在还原环境中有效地释放内容物。与Lipofectamine™2000相比,INAs在HEK 293细胞上表现出更高的转染效率和更低的细胞毒性。细胞摄取和亚细胞定位以及核转移的定量研究表明,INAs的高转染效率可能来自于DOPE介导的细胞摄取增强和PS介导的高效核递送。INAs在荷瘤裸鼠体内的生物分布表明,这种基于psd的纳米组装体装载PS/DNA可能是一种很有前景的肿瘤基因递送系统。
A new “intelligent” nanoassembly (INA), consisting of a condensed core of pDNA with protamine sulfate (PS) and a dioleoylphosphatidyl ethanolamine (DOPE)-based lipid envelope containing poly(ethylene glycol)-disulfide-DOPE (PSD), was designed and investigated. The in vitro release experiment was carried out in solution containing 10mM of Glutathione, which reflected the redox potential of the intracellular environment. The experimental result indicated that PSD possessed a good ability of self-dePEGylation and could result in efficient release of content in the reductive environment. INAs showed higher transfection efficiency and much lower cytotoxicity compared with Lipofectamine™ 2000 on HEK 293 cells. Cellular uptake and subcellular localization, as well as the quantitation of nuclear transfer demonstrated that the superior transfection efficiency of INAs could result from both enhanced cellular uptake mediated by DOPE and efficient nuclear delivery mediated by PS. The biodistribution of INAs in nude mice bearing tumor implied that this PSD-based nanoassembly loading PS/DNA could be a promising gene delivery system for tumor therapy.
DOI: 10.1038/sj.mt.6300323
发表时间: 2008-01-01
期刊: MOLECULAR THERAPY
影响因子: 12.4
作者:
Li, Shyh-Dar;Chen, Yun-Ching;Huang, Leaf
通讯作者: Huang, Leaf