Targeted delivery of antisense oligodeoxynucleotides to folate receptor-overexpressing tumor cells

被引：24

作者：

Yang, LJ ^{[1
]}

Li, J ^{[1
]}

Zhou, W ^{[1
]}

Yuan, X ^{[1
]}

Li, S ^{[1
]}

机构：

[1] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Ctr Pharmacogenet, Pittsburgh, PA 15213 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2004年 / 95卷 / 02期

关键词：

antisense; oligodeoxynucleotides; folate; targeting; lipid vector;

D O I：

10.1016/j.jconrel.2003.11.021

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A major problem in exploring the full potential of antisense ODN is the lack of a safe and efficient delivery system. In this study a new method has been developed that is highly efficient in encapsulating ODN inside folate receptor (FR)-targeted lipid vesicles. ODN formulated in these vesicles were efficiently protected from degradation by mideases compared to free ODN. Folate efficiently mediated intracellular delivery of ODN to KB tumor cells that overexpress FR. Delivery of EGFR antisense ODN via FR-targeted lipid vesicles resulted in a significant down-regulation of EGFR expression in KB cells and cell growth inhibition, far more efficient than that with free ODN or ODN encapsulated in ligand-free lipid vesicles. Intracellular delivery of EGFR antisense ODN also sensitized KB cells to doxorubicin (DOX) treatment. Thus targeted delivery of ODN via this novel lipid vector may have potential in treating tumors that overexpress FR. (C) 2004 Elsevier B.V. All rights reserved.

引用

页码：321 / 331

页数：11

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