Receptor-specific delivery of liposomes via folate-PEG-Chol

被引:73
|
作者
Guo, WJ [1 ]
Lee, T [1 ]
Sudimack, J [1 ]
Lee, RJ [1 ]
机构
[1] Ohio State Univ, Coll Pharm, Div Pharmaceut & Pharmaceut Chem, Columbus, OH 43210 USA
关键词
liposome; doxorubicin; folate receptor; drug targeting; polyethyleneglycol;
D O I
10.3109/08982100009029385
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A novel lipophilic conjugate of folate, folate-PEG-Cho1, was synthesized and evaluated for receptor-mediated targeting of liposomes to tumor cells. Liposomes composed of DSPC/Chol/PEG-DSPE/folate-PEG-Chol (60/34/5/1, m/m) were taken up by cultured folate receptor-bearing KB cells via a saturable mechanism. Cellular binding of these liposomes could be competitively inhibited by free folic acid with an IC50 Of 0.39 mM, indicating an extraordinarily high binding affinity. Fluorescence micrographs of KB cells treated with targeted liposomes encapsulating calcein showed that they were distributed both on the cell surface and in intracellular vesicular compartments. Targeted liposomes carrying doxorubicin were shown to be 38 times more toxic to KB cells than non-targeted control liposomes. A biodistribution study in receptor-positive tumor-bearing C57BL/6 mice showed no significant differences between the tumor uptake of folate-PEG-liposomes and non-targeted control liposomes. This study has demonstrated that cholesterol could be used as an alternative to phospholipids as an effective anchor for incorporation of a targeting ligand into liposomes.
引用
收藏
页码:179 / 195
页数:17
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