SELECTIVE TARGETING OF MALIGNANT-CELLS WITH CYTOTOXIN-FOLATE CONJUGATES

被引:84
作者
LEAMON, CP [1 ]
LOW, PS [1 ]
机构
[1] PURDUE UNIV,DEPT CHEM,W LAFAYETTE,IN 47907
关键词
CANCER CHEMOTHERAPY; ENDOCYTOSIS; FOLATE-BINDING PROTEIN; PROTEIN TOXINS; RECEPTOR TARGETING;
D O I
10.3109/10611869409015898
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Previous work has shown that proteins can be nondestructively delivered into the cytoplasm of folate receptor-bearing cells if the proteins are conjugated to folic acid prior to addition to cells. In view of other reports suggesting the membrane receptor for folic acid is vastly overexpressed on tumor cells, we decided to explore whether malignant cells might be selectively targeted in a coculture with nontransformed cells using ligated folate as the targeting agent. Exploiting the cytotoxicity of the ribosome-inacitivating toxin, momordin, to assay successful intracellular protein delivery, we demonstrate that HeLa and KB cells (two malignant human cell lines) can be selectively and quantitatively killed in co-cultures with WI38 and Hs67 cells (two normal human cell types). Not only are the normal cells not damaged by treatment of the co-cultures with momordin-folate, but their rates of proliferation actually accelerate, presumably due to increased availability of nutrients otherwise consumed by the transformed cells. Analysis of folate receptor number before and after momordin-folate treatment indicates that receptor density may be a good predictor of toxin-folate sensitivity. Taken together, the data suggest that conjugates of folic acid with cytotoxic proteins warrant further examination as possible tumor-specific chemotherapeutic agents.
引用
收藏
页码:101 / 112
页数:12
相关论文
共 28 条