氨氧基脂质的设计、合成及体外转染试验  

Design, Synthesis and Transfection Efficiency of Aminooxy Lipids

作　　者：张秋晨 姜发琴[1] 谢东升[1] 杨凤志 傅磊[1] ZHANG Qiuchen;JIANG Faqin;XIE Dongsheng;YANG Fengzhi;FU Lei(School of Pharmacy,Shanghai Jiaotong University,Shanghai 20024)

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《中国医药工业杂志》2018年第9期1255-1263,共9页Chinese Journal of Pharmaceuticals

基　　金：上海交通大学医学与工程学院跨学科研究基金(YG2015QN03;YG2014MS10和YG2017MS77);国家自然科学基金(81202397);上海自然科学基金(12ZR1415400)

摘　　要：为了找到一种结构简单的氨氧基辅助脂质,且能很好地适配阳离子脂质体达到高效转染目标基因的目的,本文用三缩四乙二醇、胆固醇氯甲酸酯和N-叔丁氧羰基氨氧基乙酸等经济易得的原料,合成出一种新的氨氧基脂质APCL。它是一个两端分别为氨氧基和胆固醇甲酰基,并以一条连接链连接的两亲性脂质分子。将APCL同阳离子脂质和其他辅助脂质通过薄膜分配法制成脂质体,并包裹报道基因,以另一种目前常用的氨氧基脂质CA为对照进行试验,相同条件下的体外转染数据显示,APCL阳离子脂质体运载系统比CA体系的体外转染活性更高,平均转染活性提高了3~5倍。For the purpose of finding an aminooxy helper lipid which is structural simplified and well-suited to cationic liposomes, in this paper, a new aminooxy lipid（APCL） was synthesized using the readily available starting materials such as tetraethylene glycol, cholesterol formyl chloride and 2-[[（tert-butoxycarbonyl）amino]oxy]acetic acid. APCL is an amphipathic lipid with an aminooxy and a cholesteryloxycarbonyl groups on both ends and linked by a linker. In this study, APCL, cationic lipid and other helper lipid were dissolved together to prepare cationic liposome delivery system via membrane dispersion method. After the reporter gene was packaged, the in vitro transfection experiments were carried out. Using another commonly-used aminoxy lipid CA as a control, in vitro transfection data under the same conditions showed that, APCL cationic liposome delivery system has a higher in vitro transfection activity than CA system, and the average transfection activity is increased 3-5 times..

关 键 词：阳离子脂质体 氨氧基脂质 纳米微粒 体外转染 

分 类 号：R943[医药卫生—药剂学] R914.5[医药卫生—药学]