Analytical Chemistry

Development of Rofecoxib-Based Fluorescent Probes and Investigations on Their AIE Activity, Solvatochromism, Mechanochromism and COX-2 Targeted Bioimaging

Authors

  • Lijun Xie Fujian Institute of Microbiology & University of Houston ,
  • Renfu Li Fujian Institute of Research on the Structure of Matter ,
  • Biyun Zheng Fujian Medical University Union Hospital ,
  • Zuoxu Xie University of Houston ,
  • Xuefen Fang Fujian Medical University Union Hospital ,
  • Yanqi Wang Fujian Institute of Research on the Structure of Matter ,
  • Gregory Cuny University of Houston ,
  • Zhenli Li Shenyang Pharmaceutical University ,
  • Bin Lin Shenyang Pharmaceutical University ,
  • Xueyuan Chen Fujian Institute of Research on the Structure of Matter ,
  • Ming Hu University of Houston

Abstract

Cyclooxygenase-2 (COX-2) fluorescent probes are promising tools for early cancer diagnosis. Traditionally, COX-2 probes were designed by connecting two parts, a fluorophore and a COX-2 binding unit, via a flexible linker. Herein, a new class of COX-2-specific fluorescent probes have been developed by one-step modification from rofecoxib by an integrative approach to combining the fluorophore and binding units into one. Among them, several new rofecoxib analogues not only retained their COX-2 binding ability but also exhibited attractive fluorescent properties, such as tunable Blue-Red emission, solvatochromism, AIE behavior and mechanochromism. Notably, the emission of 2a16 can be switched between greenish-yellow in the crystalline state to red-orange in the amorphous state by grinding and fuming treatments. Furthermore, the highly fluorescent compound 2a16 (Фf = 0.94 in powder) displayed much stronger fluorescent imaging of COX-2 in HeLa cancer cells overexpressing COX-2 than RAW264.7 normal cells with minimal expressing of COX-2. Most importantly, 2a16 can light up human cancer tissues from adjacent normal tissues with much brighter fluorescence by targeting COX-2 enzyme. These results illustrate the potential of 2a16 as a new red fluorescent probe for human cancer imaging in clinical applications.

Content

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Supplementary material

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Development of Rofecoxib-Based Fluorescent Probes and Investigations on Their AIE Activity, Solvatochromism, Mechanochromism and COX-2 Targeted Bioimaging
The Supporting Information to the manuscript with the same title