DELIVERY OF LIPOSOMES INTO CULTURED KB CELLS VIA FOLATE RECEPTOR-MEDIATED ENDOCYTOSIS

Folic acid was covalently conjugated to 66-nm liposomes via spacers of various lengths in an attempt to target the liposomes to KB cells exp ressing folate receptors. Spacers of short and intermediate lengths we re unable to mediate association of folate-conjugated liposomes with r eceptor-bearing cells, however, use of a 250 angstrom polyethyleneglyc ol spacer (PEG, M(r) approximately 3350) permitted avid uptake of the liposomes at approximately 2.5 x 10(5) sites/cell. The binding of fola te-PEG liposomes to KB cells could be competitively inhibited by exces s free folate or by antiserum against the folate receptor, demonstrati ng the interaction is mediated by the cell surface folate-binding prot ein. Following binding, cell-associated folate-PEG liposomes were inte rnalized by folate-receptor-mediated endocytosis at 37-degrees-C but n ot at 4-degrees-C. These folate-PEG liposomes show potential for deliv ering large quantities of low molecular weight compounds non-destructi vely into folate receptor-bearing cells.