Endosomolytic activity of cationic liposomes enhances the delivery of human immunodeficiency virus-1 transactivator protein (tat) to mammalian cells

Endosomolytic activity of cationic liposomes enhances the delivery of human immunodeficiency virus-1 transactivator protein (tat) to mammalian cells
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DOI:
10.1006/bbrc.1995.2838
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发表时间:
1995-12-26
影响因子:
3.1
通讯作者:
Barsoum, J
Barsoum, J
中科院分区:
生物学4区
文献类型:
--
作者:
Huang, L;Farhood, H;Barsoum, J

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我们已经探索了使用阳离子脂质体来提供人类免疫缺陷病毒-1反式激活蛋白达特使用报告基因表达测定。将用人免疫缺陷病毒-1启动子控制下的报告基因稳定转染的人表皮样癌细胞A431用作靶细胞。含磷脂酰胆碱的阳离子脂质体没有可检测到的达特递送活性。相比之下,使用富含二油酰磷脂酰乙醇胺(DOPE)的阳离子脂质体(一种易于将双层转化为非双层结构的脂质),达特的递送增强了150倍。通过含DOPE的脂质体增强的达特递送最可能是脂质体的内体溶解活性的结果。这种富含磷脂的制剂在足以最大递送达特的浓度下没有显示出毒性。成功地测试了多种含有DOPE的阳离子脂质体制剂用于大鼠递送。(C)出版社:Academic Press
We have explored the use of cationic liposomes to deliver the human immunodeficiency virus-1 trans-activator protein tat using a reporter gene expression assay. The human epidermoid carcinoma cell A431 stably transfected with a reporter gene under the control of human immunodeficiency virus-1 promoter was used as a target cell. Phosphatidylcholine-containing cationic liposomes had no detectable tat delivery activity. In contrast, delivery of tat was enhanced by up to 150-fold using cationic liposomes enriched with dioleoyl phosphatidylethanolamine (DOPE), a lipid which readily transforms a bilayer into a nonbilayer structure. Enhanced delivery of tat by DOPE-containing liposomes was most likely the result of the endosomolytic activity of the liposome. This phospholipid-rich formulation showed no toxicity at concentrations sufficient for maximal delivery of tat. A variety of cationic liposome formulations which contain DOPE were tested successfully for rat delivery. (C) 1995 Academic Press, Inc.