Targeted delivery of antisense oligonucleotides in cancer.
Formulations of antisense oligonucleotides (asODNs) against c-myb or c-myc protooncogenes have been prepared by a new technique that sequesters cationic lipid in the interior of a lipid particle. This technique results in high loading efficiency for the asODNs, small particle size and good stability. When targeted against melanoma cells or neuroblastoma cells via anti-GD(2) coupled at the particle surface, increased cell binding to the cells could be demonstrated. Targeted formulations showed greater inhibition of cell proliferation compared to non-targeted formulations or free drug. Inhibition of cell proliferation was demonstrated to be due to down-regulation of c-myb or c-myc protein expression. The formulations have long-circulation times in vivo, and evaluation for in vivo antitumor activity is currently underway.
Pastorino
F
F
Department of Pharmacology 9-31 MSB, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Stuart
D
D
Ponzoni
M
M
Allen
T M
TM
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008081:Liposomes; D008823:Micelles; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc