Disulfide-linked liposomes: effective delivery vehicle for Bcl-2 antisense oligodeoxyribonucleotide G3139.

Wanlop Weecharangsan, Bo Yu, Shujun Liu, Jiu Xia Pang, L James Lee, Guido Marcucci, Robert J Lee

College of Pharmacy, The Ohio State University, 542 LM Parks Hall, 500 W. 12th Ave, Columbus, OH 43210, USA.

Anticancer research 2010 Jan

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Disulfide-linked oligodeoxyribonucleotide (ODN) liposomes were formulated and evaluated for the delivery of antisense ODN G3139 in KB human oral carcinoma cells. Liposomes composed of 1,2-di-(9Z-octadecenoyl)-3-trimethylammo-nium-propane (DOTAP)/egg phosphatidylcholine/alpha-tocopheryl polyethylene glycol 1000 succinate were incorporated with hydrophobized disulfide-linked ODN. Disulfide-linked ODN liposomes were characterized for their size, ODN intracellular delivery, Bcl-2 mRNA and protein expression, growth inhibition, and chemosensitization. Intracellular delivery of ODN with disulfide-linked ODN liposomes was more efficient than that with non-liposomal hydrophobized disulfide-linked ODN. Treatment of the cells with disulfide-linked ODN liposomes resulted in efficient Bcl-2 down-regulation greater than that with hydrophobized disulfide-linked ODN and consistent with that of cellular growth inhibition and the sensitization to daunorubicin in KB cells. Disulfide-linked ODN liposomes exhibited superior colloidal stability during 5-week storage. Disulfide-linked liposomes are effective delivery vehicles for antisense ODN.

Citation

Wanlop Weecharangsan, Bo Yu, Shujun Liu, Jiu Xia Pang, L James Lee, Guido Marcucci, Robert J Lee. Disulfide-linked liposomes: effective delivery vehicle for Bcl-2 antisense oligodeoxyribonucleotide G3139. Anticancer research. 2010 Jan;30(1):31-7