The correlation between fusion capability and transfection activity in hybrid complexes of lipoplexes and pH-sensitive liposomes.
To obtain highly potent nonviral vectors with pH-sensitive fusion ability, we prepared three hybrid complexes consisting of transferrin-conjugated pH-sensitive fusogenic polymer-modified liposomes and lipoplex using three kinds of carboxylated poly(glycidol) derivatives. These hybrid complexes were stable at neutral pH, but they became fusogenic under mildly acidic conditions. Furthermore, their fusion capability varied depending on the polymer used for their preparation. Although these complexes achieved transfection of cells with higher efficiency than the parent lipoplex, the complex with higher fusion ability exhibited transfection with higher efficiency, demonstrating close correlation between the fusion ability of the complexes and their transfection activity. The hybrid complex with the highest fusion ability induced transgene expression of HeLa cells at almost 100% efficiency using enhanced green fluorescent protein gene. In addition, this complex showed much more efficient transfection than some widely used transfection reagents without cellular damage toward various human cancer-derived cell lines.
Sakaguchi
Naoki
N
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai, Osaka, Japan.
Kojima
Chie
C
Harada
Atsushi
A
Koiwai
Kazunori
K
Kono
Kenji
K
D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D008561:Membrane Fusion; D008958:Models, Molecular; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011409:Propylene Glycols / Q000737:chemistry; D014162:Transfection; D019076:Transgenes
D008081:Liposomes; D011108:Polymers; D011409:Propylene Glycols; C502907:polyglycidol