Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates

被引:377
作者
Gabizon, A [1 ]
Shmeeda, H
Horowitz, AT
Zalipsky, S
机构
[1] Hebrew Univ Jerusalem, Sch Med, Shaare Zedek Med Ctr, Dept Oncol, IL-91010 Jerusalem, Israel
[2] ALZA Corp, Mountain View, CA USA
基金
以色列科学基金会;
关键词
folate; liposome; targeting; chemotherapy; murine tumor model; PEGylation;
D O I
10.1016/j.addr.2004.01.011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Targeting of liposomes with phospholipid-anchored folate conjugates is an attractive approach to deliver chemotherapeutic agents to folate receptor (FR) expressing tumors. The use of polyethylene glycol (PEG)-coated liposomes with folate attached to the outer end of a small fraction of phospholipid-anchored PEG molecules appears to be the most appropriate way to combine long-circulating properties critical for liposome deposition in tumors and binding of liposomes to FR on tumor cells. Although a number of important formulation parameters remain to be optimized, there are indications, at least in one ascitic tumor model, that folate targeting shifts intra-tumor distribution of liposomes to the cellular compartment. In vitro, folate targeting enhances the cytotoxicity of liposomal drugs against FIR-expressing tumor cells. In vivo, the therapeutic data are still fragmentary and appear to be formulation- and tumor model-dependent. Further Studies are required to determine whether folate targeting can confer a clear advantage in efficacy and/or toxicity to liposomal drugs. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:1177 / 1192
页数:16
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