Novel gene delivery systems: complexes of fusigenic polymer-modified liposomes and lipoplexes

Abstract

We have previously developed the succinylated poly(glycidol)-modified liposome which becomes fusigenic under weakly acidic condition. In this report, we describe that complexation of this pH-sensitive, fusigenic liposome with a lipoplex consisting of 3␤-(N-(NЈ,NЈ-dimethylaminoethane) carbamoyl)cholesterol, dioleoylphosphatidylethanolamine and plasmid DNA gives efficient gene delivery systems. In this study, we prepared the complexes, which are termed SucPG-complexes, with a positively or negatively charged surface by mixing the lipoplex with varying amounts of the SucPG-modified liposomes. The positively charged SucPGcomplexes either bearing or not bearing a cell-specific

Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes

“…Transferrin or aminoethylcarbamylmethyl mannan was conjugated to SucPG or MGluPG using EDC as previously reported [14]. Briefly, to the liposome suspension was added EDC (0.…”

“…Briefly, to the liposome suspension was added EDC (0. Then, transfected cells were evaluated by luciferase assay [14].…”

“…The decreasing activities at higher N/P ratio might result from higher toxicity of the complex. This figure also shows that the SucPG complexes at the N/P ratio of 4 exhibited more efficient transfection than the parent lipoplex, indicating that the complexation of SucPG-modified liposomes was as effective for transfection of DC2.4 cells as for cancer cells [14][15][16][17]. The following assay was performed using lipoplexes and SucPG complexes at the N/P ratio of 4.…”

“…Previously, we prepared hybrid complexes comprising lipoplexes and liposomes modified with pH-sensitive fusogenic polymers, such as succinylated poly(glycidol) (SucPG) and 3-methylglutarylated poly(glycidol) (MGluPG) [14][15][16][17]. These complexes, which are designated respectively as SucPG complex and MGluPG complex, generate 7 fusion capability under mildly acidic conditions.…”

“…Consequently, once an appropriate ligand, such as transferrin, was conjugated, they achieved efficient transfection of various cancer-derived cell lines, such as HeLa and K562 cells, through efficient cellular association via receptor-mediated endocytosis and through endosomal escape via membrane fusion with endosome ( Fig. 1) [14][15][16][17].…”