FOLATE-MEDIATED TUMOR-CELL TARGETING OF LIPOSOME-ENTRAPPED DOXORUBICIN IN-VITRO

Receptors for the vitamin folic acid are frequently overexpressed on e pithelial cancer cells. To examine whether this overexpression might b e exploited to specifically deliver liposome-encapsulated drug molecul es in vitro, folate-targeted liposomes were prepared by incorporating 0.1 mol% of a yethyleneglycol-distearoylphosphatidylethanolamine (fola te-PEG-DSPE) construct into the lipid bilayer, and were loaded with do xorubicin (DOX), an anti-cancer drug. Uptake of folate-PEG-liposomal D OX by KB cells was 45-fold higher than that of non-targeted liposomal DOX, and 1.6-times higher than that of free DOX, while the cytotoxicit y was 86 and 2.7-times higher, respectively. Folate-targeting is fully compatible with PEG-coating of the liposomes, since incorporation of 4 mol% PEG2000-DSPE does not reduce the uptake or cytotoxicity of fola te-PEG-liposomal DOX. Uptake of folate-PEG-liposomes was inhibited by 1 mM free folic acid but was unaffected by physiological concentration s of folate. In HeLa/W138 co-cultures, folate-PEG-liposomes encapsulat ing calcein, a fluorescent dye, were found to be almost exclusively in ternalized by the HeLa cells which overexpress the folate receptors. W e suggest that folate targeting constitutes a possible mechanism for i mproving the specificity of PEG-coated liposomes for cancer cells.