Open AccessTargeting Gallium to Cancer Cells through the Folate Receptor
Author(s) -
Nerissa Viola-Villegas,
Anthony R. Vortherms,
Robert P. Doyle
Publication year - 2008
Publication title -
drug target insights
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.297
H-Index - 12
ISSN - 1177-3928
DOI - 10.4137/dti.s651
Subject(s) - folate receptor , chinese hamster ovary cell , dota , cell culture , gallium , ethylene glycol , cytotoxicity , in vitro , peg ratio , imaging agent , medicine , receptor , hepes , cancer , cancer research , cancer cell , pharmacology , biochemistry , chemistry , chelation , biology , in vivo , organic chemistry , microbiology and biotechnology , finance , economics , genetics
The development of gallium(III) compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III) as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III) compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA) with long chain liquid polymer poly(ethylene glycol) (PEG) 'spacers’. This FA-PEG unit has been coupled to the gallium coordination complex of 1,4,7,10-tetraazacyclo-dodecane-N, N′, N′, N′′-tetraacetic acid (DOTA) through amide linkages for delivery into target cells overexpressing the folate receptor (FR). In vitro cytotoxicity assays were conducted against a multi-drug resistant ovarian cell line (A2780/AD) that overexpresses the FR and contrasted against a FR free Chinese hamster ovary (CHO) cell line. Results are rationalized taking into account stability studies conducted in RPMI 1640 media and HEPES buffer at pH 7.4