FAP-?-Instructed Coumarin Excimer Formation for High Contrast Fluorescence Imaging of Tumor
Nano letters(2022)
摘要
Emissive excimers, which are formed by planar polycyclic aromatic fluorophores (e.g., coumarin), enable high contrast tumor imaging. However, it is still challenging to "turn on " excimer fluorescence in physiological dilute solutions. The biocompatible CBT-Cys click condensation reaction enables both intra-and intermolecular aggregations of the as-loaded fluorophores on the probe molecules, which may promote the generation of emissive excimers in a synergistic manner. As a proof-of-concept, we herein design a fluorescence probe Cbz-Gly-Pro-Cys(StBu)-Lys(coumarin)-CBT (Cbz-GPC(StBu)K(Cou)-CBT), which can be activated by FAP-alpha under tumor-inherent reduction conditions, undergo a CBT-Cys click reaction, and self-assemble into coumarin nanoparticle Cou-CBT-NP to "turn on " the excimer fluorescence. In vitro and in vivo studies validate that this "smart " probe realizes efficient excimer fluorescence imaging of FAP-alpha-overexpressed tumor cells with high contrast and enhanced accumulation, respectively. We anticipate that this probe can be applied for diagnosis of FAP-alpha-related diseases in the clinic in near future.
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关键词
CBT-Cys click reaction, Excimer, Fibroblast activation protein alpha (FAP-?), Fluorescence imaging, Self-assembly
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