Folate-targeted non-viral DNA vectors for cancer gene therapy.
The vitamin folic acid exhibits high affinity for the endocytosed, membrane-bound folate receptor. Conjugation of folic acid via its gamma-carboxyl group to various macromolecules results in binding to, and endocytosis into, cells expressing the folate receptor. The folate receptor is overexpressed on a wide range of cancers, therefore folic acid has been investigated as a targeting ligand for the specific delivery of therapeutic compounds to cancer cells. This review will introduce folate-targeting of macromolecules to cancer cells in vitro and in vivo, and discuss the accumulation of such compounds in non-target tissues in vivo. Folate-targeting of non-viral DNA vectors in vitro and in vivo will be discussed in detail, with particular emphasis on the recent advances in this field.
CRC Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham, B15 2TA, UK. wardcm@hotmail.com
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D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics*; D016503:Drug Delivery Systems; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D011956:Receptors, Cell Surface; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D004247:DNA; D005492:Folic Acid