Bisethylnorspermine lipopolyamine as potential delivery vector for combination drug/gene anticancer therapies.

PURPOSE: To design novel synthetic gene delivery system in which the carrier molecule functions dually as a carrier and a cytotoxic agent targeting dysregulated polyamine metabolism in cancer. METHODS: Bisethylnorspermine (BENSpm) lipopolyamine was synthesized and its toxicity evaluated by MTS assay in MCF-7 and MCF-10A cells. Transfection activity was determined using luciferase plasmid DNA. RESULTS: Asymmetrical lipid analogue of polyamine anticancer drug BENSpm was synthesized using nucleophilic ring opening of azetidinium ion. The synthesized LipoBENSpm showed cytotoxicity comparable to that of parent BENSpm in human breast cancer cell line MCF-7 but mediated 3-4 orders magnitude higher transfection activity. Importantly, cytostatic activity of BENSpm, typically in a low muM range, falls within a relevant and typical concentration range required for efficient gene delivery. CONCLUSIONS: These findings make gene delivery vectors based on BENSpm promising candidates for combination drug/gene approaches to the treatment of cancer.