FOLATE-MEDIATED TARGETING OF ANTINEOPLASTIC DRAGS, IMAGING AGENTS, AND NUCLEIC-ACIDS TO CANCER-CELLS

The receptor for the vitamin, folic acid, is overexpressed on a number of human tumors, including cancers of the ovary, kidney, uterus, test is, brain, colon, lung, and myelocytic blood cells. Conjugates of foli c acid linked via its gamma-carboxyl to either a single drug molecule or assembly of molecules can bind to and enter receptor-expressing can cer cells via folate receptor-mediated endocytosis. Because the affini ty of folate conjugates for cell surface folate receptors is high (K-D <similar (K-D similar to 10(-10) M), folic acid derivatization allows the selective delivery of diagnostic and therapeutic agents to cancer cells in the presence of normal cells. This review will summarize stud ies aimed at folate-mediated targeting of protein toxins, imaging agen ts, antisense oligodeoxynucleotides, genes, and liposomes specifically to cancer cells in vitro and in vivo. (C) 1998 Elsevier Science B.V.