Chen Hao, Liu Lingjun, Qian Kun, Liu Hailong, Wang Zhiming, Gao Feng, Qu Chunrong, Dai Wenhao, Lin Daizong, Chen Kaixian, Liu Hong, Cheng Zhen
State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Sci Adv. 2022 Aug 12;8(32):eabo3289. doi: 10.1126/sciadv.abo3289.
Long Stokes shift dyes that minimize cross-talk between the excitation source and fluorescent emission to improve the signal-to-background ratio are highly desired for fluorescence imaging. However, simple small molecular dyes with large Stokes shift (more than 120 nanometers) and near-infrared (NIR) emissions have been rarely reported so far. Here, inspired by the chromophore chemical structure of fluorescent proteins, we designed and synthesized a series of styrene oxazolone dyes (SODs) with simple synthetic methods, which show NIR emissions (>650 nanometers) with long Stokes shift (ranged from 136 to 198 nanometers) and small molecular weight (<450 daltons). The most promising SOD9 shows rapid renal excretion and blood-brain barrier passing properties. After functioning with the mitochondrial-targeted triphenylphosphonium (TPP) group, the resulting SOD9-TPP can be engineered for head-neck tumor imaging, fluorescence image-guided surgery, brain neuroimaging, and on-site pathologic analysis. In summary, our findings add an essential small molecular dye category to the classical dyes.
对于荧光成像而言，非常需要长斯托克斯位移染料，这种染料可使激发源与荧光发射之间的串扰最小化，从而提高信噪比。然而，迄今为止，很少有关于具有大斯托克斯位移（超过120纳米）和近红外（NIR）发射的简单小分子染料的报道。在此，受荧光蛋白发色团化学结构的启发，我们设计并合成了一系列苯乙烯恶唑啉酮染料（SODs），其合成方法简单，具有近红外发射（>650纳米）、长斯托克斯位移（范围为136至198纳米）和小分子量（<450道尔顿）。最有前景的SOD9显示出快速的肾脏排泄和血脑屏障通过特性。与线粒体靶向三苯基膦（TPP）基团作用后，所得的SOD9-TPP可用于头颈肿瘤成像、荧光图像引导手术、脑神经成像和现场病理分析。总之，我们的发现为经典染料增添了一类重要的小分子染料。
