title: Real-Time Tracking and In Vivo Visualization of β-Galactosidase Activity in Colorectal Tumor with a Ratiometric Near-Infrared Fluorescent Probe.
abstract: Development of "smart" noninvasive bioimaging probes for trapping specific enzyme activities is highly desirable for cancer therapy in vivo. Given that β-galactosidase (β-gal) is an important biomarker for cell senescence and primary ovarian cancers, we design an enzyme-activatable ratiometric near-infrared (NIR) probe (DCM-βgal) for the real-time fluorescent quantification and trapping of β-gal activity in vivo and in situ. DCM-βgal manifests significantly ratiometric and turn-on NIR fluorescent signals simultaneously in response to β-gal concentration, which makes it favorable for monitoring dynamic β-gal activity in vivo with self-calibration in fluorescent mode. We exemplify DCM-βgal for the ratiometric tracking of endogenously overexpressed β-gal distribution in living 293T cells via the lacZ gene transfection method and OVCAR-3 cells, and further realize real-time in vivo bioimaging of β-gal activity in colorectal tumor-bearing nude mice. Advantages of our system include light-up ratiometric NIR fluorescence with large Stokes shift, high photostability, and pH independency under the physiological range, allowing for the in vivo real-time evaluation of β-gal activity at the tumor site with high-resolution three-dimensional bioimaging for the first time. Our work provides a potential tool for in vivo real-time tracking enzyme activity in preclinical applications.
authors.forename: Kaizhi
authors.initials: K
authors.lastname: Gu
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Guo
authors.forename: Shaojia
authors.initials: S
authors.lastname: Zhu
authors.forename: Shiqin
authors.initials: S
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of Chemistry, University of Bath , Bath BA2 7AY, United Kingdom.
authors.forename: Tony D
authors.initials: TD
authors.lastname: James
authors.forename: He
authors.initials: H
authors.lastname: Tian
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000201:enzymology*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008819:Mice, Nude; D057054:Molecular Imaging; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry*; D059629:Signal-To-Noise Ratio; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D001616:beta-Galactosidase / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D011714:Pyrans; D001616:beta-Galactosidase