Fluorescent In Situ Targeting Probes for Rapid Imaging of Ovarian‐Cancer‐Specific γ‐Glutamyltranspeptidase

Abstract

γ-Glutamyltranspeptidase (GGT) is a tumor biomarker that selectively catalyzes the cleavage of glutamate overexpressed on the plasma membrane of tumor cells. Here, we developed two novel fluorescent in situ targeting (FIST) probes that specifically target GGT in tumor cells, which comprise 1) a GGT-specific substrate unit (GSH), and 2) a boron-dipyrromethene (BODIPY) moiety for fluorescent signalling. In the presence of GGT, sulfur-substituted BODIPY was converted to amino-substituted BODIPY, resulting in dramatic fluorescence variations. By exploiting this enzyme-triggered photophysical property, we employed these FIST probes to monitor the GGT activity in living cells, which showed remarkable differentiation between ovarian cancer cells and normal cells. These probes represent two first-generation chemodosimeters featuring enzyme-mediated rapid, irreversible aromatic hydrocarbon transfer between the sulfur and nitrogen atoms accompanied by switching of photophysical properties.

Recent Advances in the Development of Optical Imaging Probes for γ‐Glutamyltranspeptidase

“…In 2015, the group of Fan reported another intriguing ratiometric fluorescence probe ( 20 ), called a fluorescent in situ targeting (FIST) probe for GGT detection in cancer cells . In their design, GSH was directly conjugated to a fluorophore of boron‐dipyrromethene (BODIPY) to yield sulfur‐substituted BODIPY with fluorescence emission at λ =601 nm.…”

“…In 2015, the group of Fan reporteda nother intriguing ratiometric fluorescencep robe (20), called af luorescent in situ targeting (FIST) probe for GGT detection in cancer cells. [39] In their design,G SH was directly conjugated to af luorophore of boron-dipyrromethene( BODIPY) to yield sulfur-substituted BODIPYw ith fluorescencee mission at l = 601 nm. GGT-triggered cleavage of the g-Glu group in the GSH moiety could release free amino groups, which subsequently underwent intramolecular rearrangementt oy ield amino-substituted BODIPY (BODIPY-Cys) through af ive-membered cyclic transition process ( Figure 8A).…”

Autofluorescent gelatin nanoparticles as imaging probes to monitor matrix metalloproteinase metabolism of cancer cells

“…Among various bioimaging methods like (near) infrared and Raman spectroscopy, magnetic resonance imaging (MRI), radioimaging, CT imaging, positron emission tomography, and so forth, fluorescent imaging is the most widespread due to its sensitivity, selectivity and versatility . Recent advances in fluorescence imaging and probes enable us to image cellular activity in a real‐time manner, especially about those metabolic activities in cancer cells (e.g., communications, invasiveness and metastasis), which greatly helps to reveal valuable insights about cancer occurrence, development and metastasis . Commonly‐used fluorescent probes include fluorescently doped silicas and sol–gels, hydrophilic/hydrophobic polymers, quantum dots, carbon dots, upconversion nanoparticles, noble metal nanoparticles (e.g., gold or silver nanoparticles), and so on .…”

Stepwise Polychlorination of 8-Chloro-BODIPY and Regioselective Functionalization of 2,3,5,6,8-Pentachloro-BODIPY

“…1 Therefore, the development of efficient synthetic methodologies to functionalized BODIPYs has been the subject of intense research in recent years. Among these, core-halogenated BODIPYs are particularly attractive synthetic targets, since they allow the introduction of a variety of functionalities to the BODIPY core via both nucleophilic substitutions and metal-catalyzed cross-coupling reactions.…”