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Published on: December 23, 2021
A "One-to-Multi" Activatable Near-infrared Fluorescent Probe for the Sensitive Imaging of γ‑Glutamyl Transpeptidase
Yiru Ding1, Youyan Chen1, Huanke Dou1
1State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
Abstract:
γ-Glutamyl transpeptidase (GGT) is a membrane-bounded enzyme closely involved in a wide range of physiological and pathological processes. While numerous fluorescent probes have been developed to image GGT activity noninvasively, in vivo applications remain challenging. A key limitation lies in GGT's localization: activated fluorophores diffuse rapidly from sites of activation, significantly reducing contrast of image in living systems. To overcome this, we adopted the "one-to-multi" design to develop a novel NIR fluorescent probe for GGT. This probe, upon a single GGT activation, triggers a cascade of effects, including markedly reduced aqueous solubility, enhanced cellular permeability, covalent self-immobilization at the target site, and enhancement in near-infrared (NIR) fluorescence intensity. This design allows real-time and sensitive imaging of GGT activity in live cells and achieves high contrast in vivo imaging with long-lasting signal retention at tumor sites in living mice.
