Targeted delivery of antisense oligonucleotides in cancer. |
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Authors: | F Pastorino D Stuart M Ponzoni T M Allen |
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Affiliation: | Department of Pharmacology 9-31 MSB, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. |
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Abstract: | 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. |
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