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-α 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-α-overexpressed tumor cells with high contrast and enhanced accumulation, respectively. We anticipate that this probe can be applied for diagnosis of FAP-α-related diseases in the clinic in near future.

中文翻译：

---

FAP-α-指导香豆素准分子形成用于肿瘤的高对比度荧光成像

由平面多环芳族荧光团（例如香豆素）形成的发射性准分子能够实现高对比度的肿瘤成像。然而，在生理稀释溶液中“开启”准分子荧光仍然具有挑战性。生物相容的 CBT-Cys 点击缩合反应能够使探针分子上负载的荧光团在分子内和分子间聚集，这可能以协同方式促进发射准分子的产生。作为概念验证，我们在此设计了一种荧光探针 Cbz-Gly-Pro-Cys(StBu)-Lys(coumarin)-CBT ( Cbz-GPC(StBu)K(Cou)-CBT )，它可以被激活通过 FAP-α 在肿瘤固有的还原条件下，进行 CBT-Cys 点击反应，并自组装成香豆素纳米颗粒Cou-CBT-NP“打开”准分子荧光。体外和体内研究证实，这种“智能”探针实现了对 FAP-α 过表达肿瘤细胞的高效准分子荧光成像，分别具有高对比度和增强的积累。我们预计该探针可在不久的将来应用于临床诊断 FAP-α 相关疾病。