基于荧光共振能量传递机制构建可激活型近红外二区荧光探针

近红外二区荧光探针由于具有近红外二区荧光的组织穿透力深且分辨率高的优点，易于实现肿瘤的原位、高时空分辨成像。然而，肿瘤标志物激活型近红外二区荧光探针的构建面临巨大挑战，其研究处于初始阶段。本项目利用荧光共振能量传递机制（FRET），构建了几个可激活型近红外二区荧光探针，具有斯托克位移大（避免激发光干扰）、亮度高的近红外二区发光。进一步利用近红外二区荧光成像的优势和激活型探针高特异性的特点，在体实现了高灵敏、高分辨的肿瘤特征信息获取。通过本面上项目的顺利实施，创建了易于多样化的分子探针平台，建立了基于FRET机制建立可激活型近红外二区荧光探针的设计理念，为指导新一代近红外二区荧光探针的创制奠定理论基础和技术支撑。

Fluorescent probes in the second near-infrared window (NIR-II) allow high spatiotemporal resolution bioimaging with deep-tissue penetration. However, construction of tumor biomarker-activatable probes with NIR-II fluorescence is in its infancy and remains a big challenge. In this project, we report fluorescence resonance energy transfer-switchable probes that emit in NIR-II region with large Stokes shifts upon the specific activation by biomarkers, enabling precise imaging by attenuating the severe cross-talk between the excitation and emission spectra. Accurate identification of cancers is realized in vivo by full utilization of the merits of NIR-II imaging of greater tissue penetration depth and spatial resolution as well as the high specificity of activatable probes. This design strategy for construction of FRET-based NIR-II probes is generalizable for developing a wide range of activatable probes. We expect that our design approach could facilitate the development of smart activatable probes to advance the NIR-II imaging in biology and medicine.