张淑芬

个人信息Personal Information

教授

博士生导师

硕士生导师

性别:女

毕业院校:大连理工大学

学位:博士

所在单位:化工学院

学科:应用化学. 精细化工. 有机化学

办公地点:大连市高新区凌工路2号西部校区化工楼E434房间

联系方式:0411-84986265

电子邮箱:zhangshf@dlut.edu.cn

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Novel carbamate-linked quaternary ammonium lipids containing unsaturated hydrophobic chains for gene delivery.

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论文类型:期刊论文

发表时间:2018-01-01

发表刊物:Bioorganic & medicinal chemistry

收录刊物:PubMed、SCIE

卷号:26

期号:12

页面范围:3535-3540

ISSN号:1464-3391

关键字:Quaternary ammonium lipids; Hydrophobic chains; Transfection; Cytotoxicity; Gene delivery

摘要:In this paper, two novel carbamate-linked quaternary ammonium lipids (MU18: a lipid with a mono-ammonium head; GU18: a lipid with a Gemini-ammonium head) containing unsaturated hydrophobic chains were designed and synthesized. The chemical structures of the synthetic lipids were characterized by infrared spectrum, ESI-MS, 1H NMR, 13C NMR, and HPLC. For investigating the effect of unsaturation on gene delivery, the previous reported saturated cationic liposomes (MS18 and GS18) were used as comparison. Cationic liposomes were prepared by using these cationic lipids and neutral lipid DOPE at the molar ratio of 1:1. Particle sizes and zeta potentials of the cationic liposomes were studied to show that they were suitable for gene transfection. The binding abilities of the cationic liposomes were investigated by gel electrophoresis at various N/P ratios from 0.5/1 to 8/1. The results indicated that the binding ability of GU18 was much better than MU18 and the saturated cationic liposomes (MS18 and GS18). DNA transfection of these liposomes comparable to commercially available reagent (DOTAP) was achieved in vitro against Hela, HepG-2 and NCI-H460 cell lines. GU18 showed higher transfection at the N/P ratio of 3/1 than other cationic liposomes and the positive control, DOTAP. All of the liposomes presented a relatively low cytotoxicity, which was measured by MTT. Therefore, the synthetic lipids bearing unsaturated hydrophobic chains and Gemini-head could be promising candidates for gene delivery. Copyright © 2018. Published by Elsevier Ltd.