Real-Time Tracking and In Vivo Visualization of β‑Galactosidase Activity in Colorectal Tumor with a Ratiometric Near-Infrared Fluorescent Probe

• Published in: Journal of the American Chemical Society Vol. 138; no. 16; pp. 5334 - 5340
• Main Authors: Gu, Kaizhi, Xu, Yisheng, Li, Hui, Guo, Zhiqian, Zhu, Shaojia, Zhu, Shiqin, Shi, Ping, James, Tony D, Tian, He, Zhu, Wei-Hong
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.04.2016
• Subjects: Animals; beta-Galactosidase - analysis; beta-Galactosidase - chemistry; beta-Galactosidase - genetics; beta-Galactosidase - metabolism; Cell Line; Colorectal Neoplasms - diagnostic imaging; Colorectal Neoplasms - enzymology; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Humans; Hydrogen-Ion Concentration; Mice, Nude; Molecular Imaging; Pyrans - chemical synthesis; Pyrans - chemistry; Signal-To-Noise Ratio; Transfection; Xenograft Model Antitumor Assays
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.6b01705

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.