A cationic derivative of amphotericin B as a novel delivery system for antisense oligonucleotides.
A novel approach based on a plasma membrane permeability-disturbing agent was proposed as an antisense oligonucleotide delivery system. AMA, a derivative of the polyene antibiotic amphotericin B, formed a stable complex when mixed with phosphodiester oligodeoxynucleotides and enhanced the intracellular uptake of a 5' fluoresceinated anti-mdr1 20-mer into NIH-MDR-G185 cells. The nonlabeled phosphorothioate form of the oligodeoxynucleotide, complexed to AMA, inhibited P-glycoprotein expression with better efficiency and less nonspecific effects than when vectorized by Lipofectin. AMA may thus be a good agent for antisense strategy.
Garcia-Chaumont
C
C
Laboratoire de Physicochimie Biomoléculaire et Cellulaire, Université Pierre et Marie Curie, Paris, France.
Seksek
O
O
Jolles
B
B
Bolard
J
J
D016475:3T3 Cells / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002412:Cations; D002417:Cattle; D002460:Cell Line; D004337:Drug Carriers; D004355:Drug Stability; D005312:Fetal Blood; D005452:Fluoresceins / Q000378:metabolism; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002412:Cations; D004337:Drug Carriers; D005452:Fluoresceins; D016376:Oligonucleotides, Antisense; C408366:amphotericin B3-(N'-dimethylamino)propylamide; D000666:Amphotericin B