Coumarin-based near-infrared fluorogenic probes: Recent advances, challenges and future perspectives

Coumarin-based fluorogenic probes have emerged as preferred imaging tools to real-time and non-invasively monitor target analyte(s) in biological systems, due to their inherent merits of tunable optical properties, facile synthesis, excellent cell-membrane permeability, and favorable biocompatibility. Compared to natural coumarins, coumarin-based near-infrared probes (CBNPs) display improved signal-to-noise ratio and higher spatial imaging resolution. Over the past few decades, multifunctional coumarin scaffolds have been used to construct practical CBNPs for dynamically tracking cellular microenvironments, metal ions, small molecules, and biomacromolecules of interest, as well as for drug screening and disease diagnosis. Herein, the advances in the development of CBNPs from molecular engineering to biomedical applications in the last decade are reviewed. Firstly, the structure-fluorescence relationships (SFRs) of coumarin derivatives, along with diverse structural types, as well as sensing mechanisms of diverse high-performance CBNPs, are well-summarized. Next, a wide array of state-of-the-art CBNPs with various recognition fragments and sensing mechanisms, together with their biomedical applications in native living systems, are illustrated. Meanwhile, the applications of CBNPs for sensing or visualizing disease biomarkers, drug screening, assessing drug efficacy in vivo, and photothermal/photodynamic therapy are also covered. Finally, the existing challenges and future perspectives in this field are highlighted. Collectively, the information and knowledge presented here provide valuable strategies and practical cases for constructing multifunctional CBNPs, which will be very helpful for researchers to devise more versatile CBNPs tools for both fundamental and applied studies.