Real-time tracking and in vivo visualization of β-galactosidase activity in colorectal tumor with a ratiometric near-infrared fluorescent probe

Kaizhi Gu, Yisheng Xu, Hui Li, Zhiqian Guo, Shaojia Zhu, Shiqin Zhu, Ping Shi, Tony D. James, He Tian, Wei-Hong Zhu

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243 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)5334-5340
Number of pages7
JournalJournal of the American Chemical Society
Volume138
Issue number16
Early online date7 Apr 2016
DOIs
Publication statusPublished - 27 Apr 2016

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