State Key Laboratory of Analytical Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC) , Nanjing University , Nanjing 210023 , China.
Key Laboratory of Nuclear Medicine of Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi 214063 , China.
J Am Chem Soc. 2020 Feb 12;142(6):2787-2794. doi: 10.1021/jacs.9b10467. Epub 2020 Jan 28.
Near-infrared (NIR) probes are ideal for fluorescence labeling and imaging of biological targets in living animals. However, the instability of common NIR dyes hampers the construction of NIR probes bearing multiple functional components such as biomolecules for specific targeting and imaging reagents for multimodality imaging. To overcome these limitations, we designed a novel NIR scaffold bearing two terminal alkynes as clickable handles and a chloride on the heptamethine backbone that allows nucleophilic substitution with an azide to generate the third clickable handle. This unique scaffold allows for facile installation of multiple functional arms for the construction of multifunctional NIR probes. Various biomacromolecules or imaging reagents can be introduced to the NIR scaffold by sequential one-pot click reactions under biocompatible conditions. The preclickable handle chloride on the NIR backbone does not interfere with the initial click reactions, and it can be easily transformed into an azide for a following click reaction. On the basis of this unique NIR scaffold, we developed a highly efficient method to construct diverse NIR probes containing multiple functional biomolecules including peptides, antibodies, nucleic acids, and NIR/PET (positron emission tomography) dual-modality imaging probes bearing tumor-targeting groups. NIR imaging or multimodality imaging using these probes was performed on live cells or tumor models on living mice.
近红外 (NIR) 探针非常适合用于在活体动物中对生物靶标进行荧光标记和成像。然而，常见的 NIR 染料的不稳定性阻碍了构建具有多个功能组件的 NIR 探针，例如用于特定靶向的生物分子和用于多模态成像的成像试剂。为了克服这些限制，我们设计了一种新型的 NIR 支架，其带有两个末端炔烃作为可点击的手柄，以及在七甲川主链上的一个氯原子，该氯原子允许与叠氮化物进行亲核取代，从而生成第三个可点击的手柄。这种独特的支架允许轻松安装多个功能臂，用于构建多功能 NIR 探针。各种生物大分子或成像试剂可以通过在生物相容条件下的顺序一锅点击反应引入到 NIR 支架中。NIR 主链上的预点击手柄氯原子不会干扰初始点击反应，并且可以很容易地转化为叠氮化物，以进行后续的点击反应。基于这种独特的 NIR 支架，我们开发了一种高效的方法来构建多种包含多个功能生物分子的 NIR 探针，包括肽、抗体、核酸以及带有肿瘤靶向基团的 NIR/PET（正电子发射断层扫描）双模态成像探针。使用这些探针在活细胞或活体小鼠的肿瘤模型上进行了 NIR 成像或多模态成像。
