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.
Wang
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Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
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D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002352:Carrier Proteins / Q000378:metabolism; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004705:Endocytosis; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008854:Microscopy, Electron; D009696:Nucleic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011956:Receptors, Cell Surface
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D003287:Contrast Media; D058973:Folate Receptors, GPI-Anchored; D009696:Nucleic Acids; D011956:Receptors, Cell Surface; D005492:Folic Acid