State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Shanghai Institute of Technical Physics of the Chinese Academy of Sciences, Shanghai, 200083, China.
Nat Commun. 2022 Jul 2;13(1):3815. doi: 10.1038/s41467-022-31521-y.
It is highly important and challenging to develop donor-acceptor-donor structured small-molecule second near-infrared window (NIR-II) dyes with excellent properties such as water-solubility and chem/photostability. Here, we discovery an electron acceptor, 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT) with highest stability in alkaline conditions, compared with conventional NIR-II building block benzobisthiadiazole (BBT) and 6,7-diphenyl-[1,2,5] thiadiazolo[3,4-g]quinoxaline (PTQ). The sulfonated hydrophilic dye, FT-TQT, is further synthesized with 2.13-fold increased quantum yield than its counterpart FT-BBT with BBT as acceptor. FT-TQT complexed with FBS is also prepared and displays a 16-fold increase in fluorescence intensity compared to FT-TQT alone. It demonstrates real-time cerebral and tumor vessel imaging capability with µm-scale resolution. Dynamic monitoring of tumor vascular disruption after drug treatment is achieved by NIR-II fluorescent imaging. Overall, TQT is an efficient electron acceptor for designing innovative NIR-II dyes. The acceptor engineering strategy provides a promising approach to design next generation of NIR-II fluorophores which open new biomedical applications.
开发具有良好水溶性和化学/光稳定性等优异性能的供体-受体-供体结构的小分子近红外二区（NIR-II）染料非常重要且具有挑战性。在这里，我们发现了一种电子受体，6,7-二（噻吩-2-基）-[1,2,5]噻二唑并[3,4-g]喹喔啉（TQT），与传统的 NIR-II 构建块苯并双噻二唑（BBT）和 6,7-二苯基-[1,2,5]噻二唑并[3,4-g]喹喔啉（PTQ）相比，在碱性条件下具有最高的稳定性。进一步用磺酸基亲水染料 FT-TQT 合成，其量子产率比以 BBT 为受体的 FT-BBT 高 2.13 倍。FT-TQT 与 FBS 形成复合物，其荧光强度比单独的 FT-TQT 增加了 16 倍。它具有亚微米级分辨率的实时脑和肿瘤血管成像能力。通过近红外二区荧光成像实现了药物治疗后肿瘤血管破坏的动态监测。总的来说，TQT 是设计新型近红外二区染料的有效电子受体。该受体工程策略为设计新一代近红外二区荧光团提供了一种有前途的方法，为新的生物医学应用开辟了道路。
