Delivery and pathway in MCF7 cells of DNA vectorized by cationic liposomesderived from cholesterol

We have investigated the delivery and the pathway in tumoral MCF7 cells of DNA carried by liposomes prepared from (trimethyl aminoethane carbamoyl cho lesterol iodide (TMAE-Chol), a cholesterol-based cationic lipid with a quat ernary ammonium on the polar head. The structure of DNA-liposome complexes depends on the length of DNA and on the lipid-DNA charge ratio X. Spherical beads constitute fine structures of the observed complexes even when they appear as aggregates. For oligonucleotide transfer, dissociation from lipos omes after transfection, penetration of the oligonucleotides into nuclei, a nd a long resident time were observed. For plasmid transfer, a correlation between the variation in the transfection level and the ultrastructure of c omplexes was demonstrated, The results showed a cellular route of lipid/pla smid complexes from the beginning by endocytosis, entrapped into endosomes, released by the latter until entry in the perinuclear area, and then penet ration of plasmids inside the nuclei resulting in the observed expression o f the beta -galactosidase gene.