Characterization of the inhibitory effect of PEG-lipid conjugates on the intracellular delivery of plasmid and antisense DNA mediated by cationic lipid liposomes
| Autor: | Barbara Mui, Michael J. Hope, Q. F. Ahkong, Z. Wang, L.Y. Song, Q. Rong, S. Ansell |
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| Rok vydání: | 2002 |
| Předmět: |
Biophysics
Glycerophospholipids Biology Transfection Biochemistry DNA Antisense Polyethylene Glycols chemistry.chemical_compound Drug Delivery Systems Oligonucleotide PEG ratio Humans Cationic liposome Antisense Luciferases Gene transfer Cells Cultured Cell Nucleus Liposome Microscopy Confocal Poly(ethylene glycol) Phosphatidylethanolamines Vesicle Cell Biology Lipids Endocytosis Quaternary Ammonium Compounds chemistry Liposomes Drug delivery lipids (amino acids peptides and proteins) Fluorescein-5-isothiocyanate DNA HeLa Cells Plasmids |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1558(1):1-13 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/s0005-2736(01)00399-6 |
| Popis: | Poly(ethylene glycol)-lipid (PEG-lipid) conjugates are widely used in the field of liposomal drug delivery to provide a polymer coat that can confer favorable pharmacokinetic characteristics on particles in the circulation. More recently these lipids have been employed as an essential component in the self-assembly of cationic and neutral lipids with polynucleic acids to form small, stable lipid/DNA complexes that exhibit long circulation times in vivo and accumulate at sites of disease. However, the presence of a steric barrier lipid might be expected to inhibit the transfection activity of lipid/DNA complexes by reducing particle-membrane contact. In this study we examine what effect varying the size of the hydrophobic anchor and hydrophilic head group of PEG-lipids has on both gene and antisense delivery into cells in culture. Lipid/DNA complexes were made using unilamellar vesicles composed of 5 mole% PEG-lipids in combination with equimolar dioleoylphosphatidylethanolamine and the cationic lipid dioleyldimethylammonium chloride. Using HeLa and HepG2 cells we show that under the conditions employed PEG-lipids had a minimal effect on the binding and subsequent endocytosis of lipid/DNA complexes but they severely inhibited active gene transfer and the endosomal release of antisense oligodeoxynucleotides into the cytoplasm. Decreasing the size of the hydrophobic anchor or the size of the grafted hydrophilic PEG moiety enhanced DNA transfer by the complexes. |
| Databáze: | OpenAIRE |
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