Hydrogen sulfide (H₂S) has been identified as the third important gaseous transmitter after nitric oxide (NO) and carbon monoxide (CO). It plays important roles in both normal physiology conditions and the process/progress of several diseases. As a result, selective detection of tissue-specific H₂S represents an important goal to aid not only cell biology research but also disease diagnosis.

Based on the previous construction of chemical probes (Chem. Commun. 2014, 50:11735；ACS Appl. Mater. Interfaces 2014, 6:19600；Analyst 2013, 138:7087), researchers from Shanghai Institute of Materia Medica, CAS, and from East China University of Science and Technology have developed a galactosyl azidonaphthalimide probe for the selective fluorogenic imaging of hepatocellular H₂S, which sets a basis for the target-specific imaging of H₂S in the liver, the main organ that produces this gaseous transmitter.

The desired probe was synthesized by a click-coupling of alkynyl naphthalimide with azido galactoside. The presence of the azide weakens the fluorescence of naphthalimide by an ICT process, and a subsequent reduction by H₂S produces aminonaphthalimide with an enhanced fluorescence. A kinetic investigation determined that DT-Gal showed rapid fluorogenic response to H₂S, and good linearity was observed by plotting the fluorescence intensity of the probe as a function of increasing H₂S. The limit of detection of DT-Gal for H₂S was determined to be 0.78 µM. The addition of the probe to the cell lines pre-treated with H₂S leads to an evident fluorescence enhancement for the human hepatoma cell line, Hep-G2 with over-expressed asialoglycoprotein receptor (ASGPR), but only a slight fluorescence increase for other cancer cells without the receptor expression such as human colon cancer HCT116, cervix cancer HeLa and lung cancer A549. In sharp contrast, co-incubation of DT-OH, a known H₂S probe that lacks the galactosyl targeting agent, with the cells led to slight, unselective fluorescence enhancement. The data from both the ASGPR knock-down and the free galactose competition proves the assumption that the strong fluorogenic signal selectively produced by the probe in Hep-G2 cells is facilitated by ASGPR-mediated endocytosis.

This research work was accomplished by the graduate students and colleagues in CHEN Guorong’s and Li Jia’s groups. The finding has been published in Chem Commun 2015, 51:3653 (IF 6.718).

Key words, Hepatocelluar hydrogen sulfide, a galactosyl azidonaphthalimide probe, Selective fluorogenic imaging,

Contact: xphe@ecust.edu.cn; yzang@simm.ac.cn;