title: Hepatocyte-targeting single galactose-appended naphthalimide: a tool for intracellular thiol imaging in vivo.
abstract: We present the design, synthesis, spectroscopic properties, and biological evaluation of a single galactose-appended naphthalimide (1). Probe 1 is a multifunctional molecule that incorporates a thiol-specific cleavable disulfide bond, a masked phthalamide fluorophore, and a single galactose moiety as a hepatocyte-targeting unit. It constitutes a new type of targetable ligand for hepatic thiol imaging in living cells and animals. Confocal microscopic imaging experiments reveal that 1, but not the galactose-free control system 2, is preferentially taken up by HepG2 cells through galactose-targeted, ASGP-R-mediated endocytosis. Probe 1 displays a fluorescence emission feature at 540 nm that is induced by exposure to free endogenous thiols, most notably GSH. The liver-specificity of 1 was confirmed in vivo via use of a rat model. The potential utility of this probe in indicating pathogenic states and as a possible screening tool for agents that can manipulate oxidative stress was demonstrated in experiments wherein palmitate was used to induce lipotoxicity in HepG2 cells.
authors.affiliation: Department of Chemistry, Korea University, Seoul, 136-701, Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Han
authors.forename: Pil-Seung
authors.initials: PS
authors.lastname: Kwon
authors.forename: Sankarprasad
authors.initials: S
authors.lastname: Bhuniya
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Sessler
authors.forename: Chulhun
authors.initials: C
authors.lastname: Kang
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D005690:Galactose / Q000737:chemistry*; D022781:Hepatocytes; D006801:Humans; D008297:Male; D051379:Mice; D053644:Naphthalimides / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D053644:Naphthalimides; D013438:Sulfhydryl Compounds; D005690:Galactose