Cationic lipids delay the transfer of plasmid DNA to lysosomes.
Plasmid 35S DNA, naked or associated with different cationic lipid preparations was injected to rats. Subcellular distribution of radioactivity in the liver one hour after injection, was established by centrifugation methods. Results show that at that time, 35S DNA has reached lysosomes. On the contrary, when 35S DNA was complexed with lipids, radioactivity remains located in organelles whose distribution after differential and isopycnic centrifugation, is clearly distinct from that of arylsulfatase, lysosome marker enzyme. Injection of Triton WR 1339, a specific density perturbant of lysosomes, four days before 35S DNA injection causes a density decrease of radioactivity bearing structures, apparent one hour after naked 35S DNA injection but visible only after more than five hours, when 35S DNA associated with a cationic lipid is injected. These observations show that cationic lipids delay the transfer to lysosomes, of plasmid DNA taken up by the liver.
Wattiaux
R
R
Laboratoire de Chimie Physiologique, Facultés Universitaires Notre-Dame de la Paix, Bruxelles, Namur, Belgium.
Jadot
M
M
Laurent
N
N
Dubois
F
F
Wattiaux-De Coninck
S
S
D000818:Animals; D001192:Arylsulfatases / Q000032:analysis; D015415:Biomarkers; D002458:Cell Fractionation; D003902:Detergents; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D015388:Organelles / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017208:Rats, Wistar; D013462:Sulfur Radioisotopes
D015415:Biomarkers; D003902:Detergents; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D013462:Sulfur Radioisotopes; D011092:Polyethylene Glycols; D001192:Arylsulfatases; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; C016811:tyloxapol