Fluorescent In Situ Targeting Probes for Rapid Imaging of Ovarian-Cancer-Specific γ-Glutamyltranspeptidase.
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.
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science & Technology, Shanghai 200237 (China).
Feiyi
F
Wang
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China).
Ying
Y
Zhu
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai 200237 (P. R. China).
Li
L
Zhou
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China).
Liang
L
Pan
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China).
Zhifen
Z
Cui
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science & Technology, Shanghai 200237 (China).
Qiang
Q
Fei
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science & Technology, Shanghai 200237 (China).
Sihang
S
Luo
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China).
Dun
D
Pan
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China).
Qing
Q
Huang
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science & Technology, Shanghai 200237 (P. R. China).
Rui
R
Wang
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science & Technology, Shanghai 200237 (China). zhaocchang@ecust.edu.cn.
Chunchang
C
Zhao
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science & Technology, Shanghai 200237 (China).
He
H
Tian
Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China). fchh@sinap.ac.cn.
Chunhai
C
Fan
D001896:Boron Compounds / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D057075:Enzyme Assays / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D061848:Optical Imaging / Q000379:methods*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000201:enzymology*; D010053:Ovary / Q000201:enzymology; D011162:Porphobilinogen / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000032:analysis* / Q000378:metabolism
D001896:Boron Compounds; D005456:Fluorescent Dyes; C507544:dipyrromethene; D011162:Porphobilinogen; D005723:gamma-Glutamyltransferase
aromatic hydrocarbon transfer; enzymes; fluorescence; photophysics; tumor cells