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

A novel lipophilic conjugate of folate, folate-PEG-Cho1, was synthesized an d evaluated for receptor-mediated targeting of liposomes to tumor cells. Li posomes composed of DSPC/Chol/PEG-DSPE/folate-PEG-Chol (60/34/5/1, m/m) wer e taken up by cultured folate receptor-bearing KB cells via a saturable mec hanism. Cellular binding of these liposomes could be competitively inhibite d by free folic acid with an IC50 Of 0.39 mM, indicating an extraordinarily high binding affinity. Fluorescence micrographs of KB cells treated with t argeted liposomes encapsulating calcein showed that they were distributed b oth on the cell surface and in intracellular vesicular compartments. Target ed liposomes carrying doxorubicin were shown to be 38 times more toxic to K B cells than non-targeted control liposomes. A biodistribution study in rec eptor-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.