胆固醇嵌入式阳离子脂质体运载基因研究  

The Development of Cholesterol Embedded Cationic Liposomes for Gene Transfer

作　　者：赵轶男[1,2] 张树彪[2] 崔韶晖[2] 张淑芬[1] 

机构地区：[1]大连理工大学精细化工国家重点实验室,大连116012 [2]大连民族学院生物技术与资源利用国家民委–教育部重点实验室,大连116600

出　　处：《中国细胞生物学学报》2014年第9期1257-1261,共5页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:20876027;21176046);国家高新技术研究发展计划(批准号:2014AA020707);中央高校自主科研基金(批准号:DC12010104)资助的课题~~

摘　　要：阳离子脂质体是一种有临床应用潜力的抗肿瘤药物递药系统,助类脂能起到稳定双层膜和降低阳性成分毒性的作用,同时提供阳性类脂的细胞渗透功能。为了进一步发掘助类脂的应用潜力,该文采用胆固醇（cholesterol）作为助类脂制备阳离子脂质体,测定了脂质体的粒径及Zeta电位,脂质体的平均粒径为100-140 nm,Zeta电位为45-60 mV。脂质体分别与绿色荧光蛋白基因（pGFP-N2）、荧光素酶基因（pGL3）结合,形成脂质体/DNA复合物,通过载入人喉癌细胞（Hep-2）,考察了其转染效率和细胞毒性。结果表明,阳离子类脂与胆固醇以1：1、1：2和1：4摩尔比例混合制备脂质体均能高效转染Hep-2细胞。毒性实验显示,阳离子类脂单独存在时对癌细胞具有一定的细胞毒性,随着胆固醇的加入,脂质体对细胞的毒性明显减小,与商品试剂DOTAP和Lipofectamine 2000相当。The cationic liposomes are a kind of anti-tumor drug delivery systems with potential clinical applications. Co-lipids can stabilize the double membrane of cationic liposomes, reduce the toxicity of cationic lipids, and improve cell penetration of cationic lipids. In this article, cholesterol was chosen to prepare cationic liposomes. The size, zeta potential and morphology of cationic liposomes were determined. The sizes of these liposomes were from 100 to 140 nm. Zeta potentials were in the range of 45-60 mV. Lipoplexes formed by the combination of cationic liposomes with pGFP-N2 and pGL3 were evaluated in terms of gene-transferring efficiency and cytotoxicity in Hep-2 cells. Our results convincingly demonstrated that cholesterol embedded cationic liposomes could condense DNA to form lipoplexes. The results showed high transfection efficiency in Hep-2 cells at the ratios of lipid to cholesterol 1：1, 1：2 and 1：4. Toxicity experiments showed that the cytotoxicity of lipids against cells increased, while cholesterol could reduce the cytotoxicity of liposomes to some extent.

关 键 词：阳离子脂质体 胆固醇 基因转运 细胞毒性 

分 类 号：R943[医药卫生—药剂学]