Endosomolytic activity of cationic liposomes enhances the delivery of human immunodeficiency virus-1 trans-activator protein (TAT) to mammalian cells.
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 tat delivery.
Huang
L
L
Department of Pharmacology, University of Pittsburgh, School of Medicine, PA 15261, USA.
Farhood
H
H
Serbina
N
N
Teepe
A G
AG
Barsoum
J
J
D002412:Cations; D016503:Drug Delivery Systems; D004705:Endocytosis; D011992:Endosomes / Q000737:chemistry; D015696:Gene Products, tat / Q000008:administration & dosage*; D015497:HIV-1; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D054322:tat Gene Products, Human Immunodeficiency Virus
D002412:Cations; D015696:Gene Products, tat; D008081:Liposomes; D054322:tat Gene Products, Human Immunodeficiency Virus