Folate-mediated targeting of antineoplastic drugs, 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, testis, brain, colon, lung, and myelocytic blood cells. Conjugates of folic acid linked via its gamma-carboxyl to either a single drug molecule or assembly of molecules can bind to and enter receptor-expressing cancer cells via folate receptor-mediated endocytosis. Because the affinity of folate conjugates for cell surface folate receptors is high (KD approximately 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 studies aimed at folate-mediated targeting of protein toxins, imaging agents, antisense oligodeoxynucleotides, genes, and liposomes specifically to cancer cells in vitro and in vivo.