高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (02): 404.doi: 10.3969/j.issn.0251-0790.2012.02.034

• 高分子化学 • 上一篇    下一篇

巯基化透明质酸包封的仿生交联基因微载体的构建

徐志学, 李文宇, 杨露, 唐三, 胡巧玲, 王幽香   

  1. 教育部高分子合成与功能构造重点实验室, 浙江大学高分子科学与工程学系, 杭州 310027
  • 收稿日期:2011-03-17 出版日期:2012-02-10 发布日期:2012-01-13
  • 通讯作者: 王幽香, 女, 博士, 副教授, 主要从事生物医用高分子材料研究. E-mail: yx_wang@zju.edu.cn E-mail:yx_wang@zju.edu.cn
  • 基金资助:

    国家自然科学基金(批准号: 50873089, 21074110)、浙江省科技计划项目(批准号: 2010C31025)、浙江省自然科学基金(批准号: Y4100101)和中央高校基本科研业务费专项(批准号: 2011QNA4025)资助.

Construction of Biomimetic Cross-linking Polyplexes with Thiolated-HA Shielding

XU Zhi-Xue, YANG Lu, TANG San, HU Qiao-Ling, WANG You-Xiang   

  1. Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
  • Received:2011-03-17 Online:2012-02-10 Published:2012-01-13
  • Contact: WANG You-Xiang E-mail:yx_wang@zju.edu.cn

摘要: 采用超分子组装技术, 通过巯基化透明质酸(HA-SH)与聚乙烯亚胺(PEI)/DNA缔合体的界面静电组装, 构建了壳层二硫键仿生交联的基因超分子组装体(PEI/DNA/HA-SH). 凝胶电泳结果表明, 该组装体有很好的DNA缔合特性. 壳层的仿生交联使基因超分子组装体在生理盐溶液中的稳定性得到有效改善, 细胞毒性显著降低, 并能有效转染细胞, 为非病毒基因传递体系的设计提供了新途径.

关键词: 非病毒基因载体, 仿生交联基因微载体, 超分子组装, 聚乙烯亚胺, 透明质酸

Abstract: The preparation of biomimetic cross-linking polyplexes was an effective way to solve the contradiction between extracellular stability and intracellular dissociation of polyplexes. In this research, thiolated-HA(hyaluronic acid) was synthesized and then added to PEI[poly(ethleneimine)]/DNA polyplexes. Due to the electrostatic attraction, cross-linking polyplexes via disulfide bonds were constructed. Gel retardation assay indicated that these ternary polyplexes showed efficient DNA condensation ability. The biomimetic cross-linking shell improved the stability in physiological salt condition. The in vitro cell culture indicated that the cross-linking polyplexes reduced cytotoxicity and showed efficient transfection efficiency. This facile approach to constructing biomimetic cross-linking polyplexes might have great potential application in non-viral gene delivery research.

Key words: Non-viral gene vector, Biomimetic cross-linking polyplex, Supramolecular assembly, Poly(ethy-leneimine)(PEI), Hyaluronic acid(HA)

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