Hepatocyte-targeting single galactose-appended naphthalimide: A tool for intracellular thiol imaging in vivo

Min Hee Lee, Ji Hye Han, Pil Seung Kwon, Sankarprasad Bhuniya, Jin Young Kim, Jonathan L. Sessler, Chulhun Kang, Jong Seung Kim

Research output: Contribution to journalArticle

294 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1316-1322
Number of pages7
JournalJournal of the American Chemical Society
Volume134
Issue number2
DOIs
Publication statusPublished - 2012 Jan 18

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Naphthalimides
Galactose
Sulfhydryl Compounds
Hepatocytes
Imaging techniques
Hep G2 Cells
Oxidative stress
Fluorophores
Asialoglycoprotein Receptor
Liver
Rats
Palmitates
Screening
Animals
Endocytosis
Experiments
Fluorescence
Ligands
Cells
Disulfides

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Hepatocyte-targeting single galactose-appended naphthalimide : A tool for intracellular thiol imaging in vivo. / Lee, Min Hee; Han, Ji Hye; Kwon, Pil Seung; Bhuniya, Sankarprasad; Kim, Jin Young; Sessler, Jonathan L.; Kang, Chulhun; Kim, Jong Seung.

In: Journal of the American Chemical Society, Vol. 134, No. 2, 18.01.2012, p. 1316-1322.

Research output: Contribution to journalArticle

Lee, Min Hee ; Han, Ji Hye ; Kwon, Pil Seung ; Bhuniya, Sankarprasad ; Kim, Jin Young ; Sessler, Jonathan L. ; Kang, Chulhun ; Kim, Jong Seung. / Hepatocyte-targeting single galactose-appended naphthalimide : A tool for intracellular thiol imaging in vivo. In: Journal of the American Chemical Society. 2012 ; Vol. 134, No. 2. pp. 1316-1322.
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