CATIONIC LIPOSOMES COATED WITH POLYETHYLENE-GLYCOL AS CARRIERS FOR OLIGONUCLEOTIDES

Modification of liposome surface with polyethylene glycol was used to improve oligodeoxyribonucleotide (ODN) loading, stability of the resul ting complexes, and specificity of cellular delivery of ODN by cationi c liposomes. Liposomes composed of a cationic lipid (DOTAP, DOGS, DDAB ), a neutral lipid (DOPE), and a phospholipid derivative of polyethyle ne glycol (PEG-PE) formed a complex with 18-mer phosphorothioate up to ODN/lipid molar ratio of 0.25, The complexes showed intact vesicular structures similar to original liposomes and their size (100-130 nm) w as unchanged after several weeks of storage, whereas complexes lacking PEG-PE showed progressive aggregation and/or precipitation. After exp osure to human plasma, PEG-modified cationic liposomes retained over 6 0% of the originally bound ODN, PEG-coated complexes resulted in 4-13- fold enhancement of the ODN uptake by human breast cancer cells in ser um-supplemented growth medium, relative to free ODN, Complexes contain ing conjugated anti-HER2 F(ab') fragments at the distal termini of PEG chains efficiently delivered ODN primarily irate che cytoplasm and nu clei of HERS overexpressing cancer cells and greatly enhanced the biol ogical activity of antisense ODN. The development of PEG-modified cati onic liposomes may lead to improved ODN potency in vivo.