ja210065g_si_001.pdf (1.37 MB)
Hepatocyte-Targeting Single Galactose-Appended Naphthalimide: A Tool for Intracellular Thiol Imaging in Vivo
journal contribution
posted on 2012-01-18, 00:00 authored by Min Hee Lee, Ji Hye Han, Pil-Seung Kwon, Sankarprasad Bhuniya, Jin Young Kim, Jonathan
L. Sessler, Chulhun Kang, Jong Seung KimWe 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.