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.
Ward
C M
CM
CRC Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham, B15 2TA, UK. wardcm@hotmail.com
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