二硫键连接脂质体：Bcl-2 反义寡脱氧核苷酸 G3139 的有效递药载体。
Disulfide-linked liposomes: effective delivery vehicle for Bcl-2 antisense oligodeoxyribonucleotide G3139.
机构信息
College of Pharmacy, The Ohio State University, 542 LM Parks Hall, 500 W. 12th Ave, Columbus, OH 43210, USA.
出版信息
Anticancer Res. 2010 Jan;30(1):31-7.
BACKGROUND
Disulfide-linked oligodeoxyribonucleotide (ODN) liposomes were formulated and evaluated for the delivery of antisense ODN G3139 in KB human oral carcinoma cells.
MATERIALS AND METHODS
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.
RESULTS
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.
CONCLUSION
Disulfide-linked liposomes are effective delivery vehicles for antisense ODN.
背景
本文制备并评价了二硫键连接的寡脱氧核苷酸（ODN）脂质体，用于递送反义寡核苷酸 G3139 在 KB 人口腔癌细胞中的作用。
材料与方法
脂质体由 1,2-二（9Z-十八烯酰基）-3-三甲基铵丙烷（DOTAP）/卵磷酯/α-生育酚聚乙二醇 1000 琥珀酸组成，并与疏水性二硫键连接的 ODN 结合。对二硫键连接的 ODN 脂质体的大小、ODN 细胞内递呈、Bcl-2mRNA 和蛋白表达、生长抑制和化疗增敏作用进行了表征。
结果
用二硫键连接的 ODN 脂质体转染 ODN 的细胞内递呈效率高于非脂质体疏水性二硫键连接的 ODN。用二硫键连接的 ODN 脂质体处理细胞可有效下调 Bcl-2，下调程度大于疏水性二硫键连接的 ODN，与 KB 细胞的细胞生长抑制和柔红霉素增敏作用一致。二硫键连接的脂质体在 5 周的储存过程中表现出优异的胶体稳定性。
结论
二硫键连接的脂质体是反义寡核苷酸的有效递药载体。
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