Cationic steroid antibiotics demonstrate DNA delivery properties.
Recently, cationic steroids have been developed that display broad-spectrum antibacterial activity. These compounds, characterized by the presence of several amino groups, present a facially amphiphilic morphology. Formulations containing such steroids were tested for their ability to facilitate the uptake of a reporter plasmid into various cell lines. The results show that, when associated with the naturally occurring zwitterionic lipid dioleoyl-phosphatidylethanolamine (DOPE), cationic steroid antibiotics allow for transfection levels comparable to those obtained with DOTAP. The activity of the amphiphilic mixture was nearly unaffected by bafilomycin A1 and chloroquine treatment, suggesting a mechanism that is independent of the acidification process associated with endocytosis. Collectively, our results show that DNA delivery agents possessing strong antibacterial properties can be obtained by conjugating amino groups to a steroid nucleus.
Kichler
Antoine
A
Genethon - UMR 8115 CNRS, 1bis rue de l'Internationale, BP 60, F-91002 Evry, France. akich@genethon.fr
Leborgne
Christian
C
Savage
Paul B
PB
Danos
Olivier
O
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010957:Plasmids; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013256:Steroids / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D014162:Transfection
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D005229:Fatty Acids, Monounsaturated; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D013256:Steroids; D004247:DNA; D008156:Luciferases; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane