Supramolecular self-assembly for delivery of oligonucleotides and its phototriggered unpacking in living cells  

超分子组装用于寡聚核苷酸的输送及其在细胞中的光诱导释放(英文)

作　　者：王鹏[1] 纪玉卓 王志轩[1] 汤新景[1,2] 

机构地区：[1]北京大学医学部天然药物及仿生药物国家重点实验室,北京100191 [2]南京大学医药生物技术国家重点实验室,江苏南京210093

出　　处：《Journal of Chinese Pharmaceutical Sciences》2014年第7期454-462,共9页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.21372018);the National Basic Research Program of China(973 Program,Grant No.2013CB933800);Program for New Century Excellent Talents in University(Grant No.NCET-10-0203);the State Key Laboratory of Pharmaceutical Biotechnology(Grant No.KF-GN-201305)

摘　　要：Two photolabile amphiphilic supramolecules were designed and synthesized with mono-dendrite and tri-dendrite, which can reversibly self-assemble to spheroid and wedge-shaped nanoparticles. With multiple branches of terminal amine labeled PEG, these nanoparticles can associate with a negatively charged oligonucleotide and their usage for oligonucleotide delivery was evaluated. Oligonucleotide/nanoparticle complex containing tri-dendrite can efficiently deliver oligonucleotide into cells via endocytosis, while the complex containing mono-dendrite almost lost their ability to deliver oligonucleotide. Further light activation triggered the dissociation of tri-dendrite supramolecular assembly via 1,4- and 1,6-quinone-methide rearrangement, leading to the efficient unpacking of the oligonucleotide in cells.本文设计合成了两种光敏的双亲性分子,分别具有单齿和三齿的结构,这两种双亲性分子可自组装成球形和楔形超分子纳米粒。超分子外部带有氨基的PEG片段可以通过静电作用与核酸结合。本文对超分子输送寡聚核苷酸进入细胞的效果进行了评价。结果表明,具有三齿结构的分子与核酸形成的复合物通过内吞作用可以有效地将核酸输送进入细胞,而单齿结构的复合物却几乎不具有此能力。给予光照后,三齿的超分子发生醌甲基化重排而解离,从而释放核酸。

关 键 词：Photo-activation SUPRAMOLECULE SELF-ASSEMBLY Oligonucleotide delivery Nucleic acid unpacking 

分 类 号：R915[医药卫生—微生物与生化药学]