title: Light induced drug release from a folic acid-drug conjugate.
abstract: A major area of cancer research focuses on improving the specificity of therapeutic agents by engineering drug-delivery vehicles that target overexpressed receptors on tumor cells. One of the most commonly used approaches involves targeting of folate receptors using folic acid conjugated to a drug-containing macromolecular cargo. Once internalized via endocytosis, the drugs must be released from these constructs in order to avoid being trapped in the endosomes. Here, we describe the synthesis of a small-molecule conjugate that couples folic acid to doxorubicin via a photocleavable linker. Using HPLC we show that the doxorubicin can be released with light rapidly and with high efficiency. This approach has advantages over macromolecular systems due to its simplicity and efficiency.
authors.affiliation: The Massey Cancer Center, 401 College St., Richmond, VA 23298-0037, USA; Department of Internal Medicine, Virginia Commonwealth University, 1101 E. Marshall St., Richmond, VA 23298, USA.
authors.forename: M Michael
authors.initials: MM
authors.lastname: Dcona
authors.affiliation: The Massey Cancer Center, 401 College St., Richmond, VA 23298-0037, USA; Department of Chemistry, Virginia Commonwealth University, 1001 West Main St., Richmond, VA 23284, USA.
authors.forename: Jonathon E
authors.initials: JE
authors.lastname: Sheldon
authors.affiliation: The Massey Cancer Center, 401 College St., Richmond, VA 23298-0037, USA; Department of Chemistry, Virginia Commonwealth University, 1001 West Main St., Richmond, VA 23284, USA.
authors.forename: Deboleena
authors.initials: D
authors.lastname: Mitra
authors.affiliation: The Massey Cancer Center, 401 College St., Richmond, VA 23298-0037, USA; Department of Chemistry, Virginia Commonwealth University, 1001 West Main St., Richmond, VA 23284, USA. Electronic address: mchartman@vcu.edu.
authors.forename: Matthew C T
authors.initials: MC
authors.lastname: Hartman
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation / Q000528:radiation effects*; D005492:Folic Acid / Q000737:chemistry*; D010782:Photolysis / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D004317:Doxorubicin; D005492:Folic Acid
keywords: Drug release; Endosomal entrapment; Folic acid; HPLC; Photocage