Enhancement of dendrimer-mediated transfection using synthetic lung surfactant exosurf neonatal in vitro.
Pulmonary surfactants enhance adenovirus-mediated gene transfer but inhibit cationic liposome-mediated transfection in lung epithelial cells in vitro. This study examines the effect of the synthetic lung surfactant Exosurf on dendrimer-mediated transfection in eukaryotic cells. Exosurf significantly enhanced dendrimer-luciferase plasmid transfection in a number of cell lines and was very effective in primary cells. Luciferase expression increased up to 40-fold in primary normal human bronchial/tracheal epithelial cells (NHBE). FACScan analysis demonstrated that the transfection rate of the human T cell leukemia Jurkat cell line has significantly improved from 10 to 90% of cells at 24 h after transfection. Analysis of the components of Exosurf revealed that the nonionic surfactant tyloxapol was responsible for the enhancement of dendrimer-mediated gene transfer. The tyloxapol effect was due to increased cell membrane porosity and DNA uptake. Our results demonstrate that Exosurf and its component, tyloxapol, constitute a powerful enhancer for dendrimer-mediated gene transfer in vitro.
Kukowska-Latallo
J F
JF
Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, 48109-064.
Chen
C
C
Eichman
J
J
Bielinska
A U
AU
Baker
J R
JR
D000818:Animals; D001980:Bronchi / Q000166:cytology; D002463:Cell Membrane Permeability; D004338:Drug Combinations; D011992:Endosomes / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005233:Fatty Alcohols / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D006801:Humans; D017403:In Situ Hybridization; D019169:Jurkat Cells; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000494:pharmacology; D013552:Swine; D014162:Transfection / Q000187:drug effects*
D004338:Drug Combinations; D005233:Fatty Alcohols; D008164:Luminescent Proteins; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents; D010767:Phosphorylcholine; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; D008156:Luciferases; C016811:tyloxapol