title: A two-photon fluorescent sensor revealing drug-induced liver injury via tracking γ-glutamyltranspeptidase (GGT) level in vivo.
abstract: Currently drug-induced liver injury (DILI) has become a major and challenging public health issue in terms of medicine development and clinical therapy. The level of γ-glutamyl transpeptidase (GGT) has long been regarded as a preclinical/clinical biomarker for prediction of DILI. Herein, we report a two-photon fluorescent sensor for tracking GGT level changes resulted from DILI in vivo. The sensor was prepared by linking a glutamic acid to a dicyanomethylene-4H-pyran (DCM) derivative; and the presence of GGT cleaves γ-glutamyl amide group from the sensor and thereby restores the fluorescence emission (at 635 nm) of DCM moiety under femtosecond pulses at 800 nm. This two-photon sensor exhibits superior sensing performance such as red emission, high photostability and low detection limit (∼0.057 U/L). On a two-photon microscope, the sensor shows a bright red fluorescence in GGT-overexpressing A2780 cells; and it can fluorescently respond to the GGT generated in the liver of zebrafishes as a result of clinical drug (phenytoin) treatment. These findings demonstrate that a commonly-used clinical drug phenytoin can cause remarkable elevation in GGT level in liver, and this sensor may be useful as a marker to detect clinical drug-induced organ damages.
authors.affiliation: College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology (SCUT), Guangzhou, 510640, PR China.
authors.forename: Peisheng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology (SCUT), Guangzhou, 510640, PR China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Jiang
authors.affiliation: College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology (SCUT), Guangzhou, 510640, PR China.
authors.forename: Xuezheng
authors.initials: X
authors.lastname: Nie
authors.affiliation: College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology (SCUT), Guangzhou, 510640, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology (SCUT), Guangzhou, 510640, PR China. Electronic address: mcfzeng@scut.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Zeng
authors.affiliation: College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology (SCUT), Guangzhou, 510640, PR China.
authors.forename: Xitao
authors.initials: X
authors.lastname: Xia
authors.affiliation: College of Materials Science and Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology (SCUT), Guangzhou, 510640, PR China. Electronic address: shzhwu@scut.edu.cn.
authors.forename: Shuizhu
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton; D010672:Phenytoin; D011714:Pyrans / Q000737:chemistry*; D015027:Zebrafish; D005723:gamma-Glutamyltransferase / Q000032:analysis* / Q000097:blood
chemical_list: D005456:Fluorescent Dyes; D011714:Pyrans; D010672:Phenytoin; D005723:gamma-Glutamyltransferase
keywords: Fluorescence; GGT activity; Liver injury; Two-photon imaging; Zebrafish