A unique off−on near-infrared cyanine-based probe for imaging of endogenous alkaline phosphatase activity in cells and in vivo

Zhiwei Gao【高志伟】^a,b, Jingya Sun^a , Min Gao【高敏】^a,c, Fabiao Yu【于法标】*^a,b, Lingxin Chen【陈令新】*^a,b, Qingguo Chen【陈庆国】*^a

^a College of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316004, China

^b Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Research Center for Coastal Environmental Engineering and Technology, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China

^c University of Chinese Academy of Sciences, Beijing 100049, China.

*E-mail: fbyu@yic.ac.cn (F. Yu); lxchen@yic.ac.cn (L. Chen); qgchen@zjou.edu.cn (Q. Chen).

Abstract: Alkaline phosphatase (ALP) is a class of enzymes that are widely found in various tissues of the human body. It plays important roles in regulating diverse cellular functions. The aberrant levels of serum ALP are implicated in diseases. The development of sensitive and accurate detection tool for evaluating the level changes of ALP in living organisms will be very helpful in the fields of biochemistry, cytology and clinical medicine. Herein, we develop a near-infrared probe (QcyP) for the specific detection of different ALP levels both in different cell lines and in tumor-bearing mice models. The probe is composed of two moieties: a unique heptamethine cyanine fluorophore and a phosphate monoester. ALP can trigger an off-on fluorescence switch via an enzyme-catalyzed cleavage of the phosphate group. The fluorescence regulation mechanism is based on the rearrangement of the conjugated π-electron system. The probe exhibits high selectivity and good sensitivity towards ALP. The results demonstrate that the probe QcyP not only can be applied to discriminate the levels of ALP in different cell lines, but also can distinguish the ALP level changes between hepatic tumor mice model and normal mice.

Key words: Alkaline phosphatase, Fluorescent probes, Near-infrared fluorescence, In vivo imaging

Sensors and Actuators B: Chemical  Volume 265, 15 July 2018, Pages 565-574 https://www.sciencedirect.com/science/article/pii/S0925400518305689