Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
Theranostics. 2020 Jan 12;10(5):2130-2140. doi: 10.7150/thno.39673. eCollection 2020.
Near-infrared (NIR) fluorescence imaging has been proved as an effective modality in identifying the tumor border and distinguishing the tumor cells from healthy tissue during the oncological surgery. Developing NIR fluorescent probes with high tumor to background (T/B) signal is essential for the complete debulking of the tumor, which will prolong the survival rate of tumor patients. However, the nonspecific binding and "always-on" properties of the conventional fluorescent probes leads to high background signals and poor specificity. : To address this problem, glutathione (GSH)-responsive, two disulfide-bonded dicyanine dyes ( and ) were synthesized. As synthesized dyes are quenched under normal physiological conditions, however, once reached to the tumor site, these dyes are capable of emitting strong fluorescence signals primarily because of the cleavage of the disulfide bond in the tumor microenvironment with high GSH concentration. Besides, the GSH-responsive behavior of these dyes was monitored using the UV-vis and fluorescence spectroscopy. The diagnostic accuracy of the aforementioned dyes was also tested both in tumor cells and 4T1-bearing mice. : The fluorescence signal intensity of disulfide dicyanine dyes was quenched up to 89% compared to the mono cyanine dyes, thus providing a very low fluorescence background. However, when the disulfide dicyanine dye reaches the tumor site, the dicyanine is cleaved by GSH into two mono-dyes with high fluorescence strength, thus producing strong fluorescent signals upon excitation. The fluorescent signal of the dicyanine was enhanced by up to 27-fold after interacting with the GSH solution. xenografts tumor studies further revealed that the fluorescence signals of aforementioned dyes can be quickly recovered in the solid tumor. : In summary, the disulfide dicyanines dyes can provide a promising platform for specific tumor-activatable fluorescence imaging with improved T/B value.
近红外（NIR）荧光成像是一种有效的方法，可用于在肿瘤手术过程中识别肿瘤边界并将肿瘤细胞与健康组织区分开来。开发具有高肿瘤与背景（T/B）信号的近红外荧光探针对于完全清除肿瘤至关重要，这将延长肿瘤患者的生存率。然而，传统荧光探针的非特异性结合和“始终开启”特性导致背景信号高且特异性差。
为了解决这个问题，合成了谷胱甘肽（GSH）响应的两个二硫键键合的二氰染料（和）。在正常生理条件下，合成的染料处于淬灭状态，但是一旦到达肿瘤部位，这些染料就能够发射出强烈的荧光信号，主要是因为在高 GSH 浓度的肿瘤微环境中，二硫键被切断。此外，还使用紫外可见和荧光光谱监测了这些染料的 GSH 响应行为。还在肿瘤细胞和 4T1 荷瘤小鼠中测试了上述染料的诊断准确性。
与单氰染料相比，二硫键二氰染料的荧光信号强度猝灭了 89%，从而提供了非常低的荧光背景。然而，当二硫键二氰染料到达肿瘤部位时，二氰染料被 GSH 切割成两个荧光强度高的单染料，因此在激发时会产生强烈的荧光信号。二氰染料与 GSH 溶液相互作用后，荧光信号增强了 27 倍。
进一步的异种移植肿瘤研究表明，上述染料的荧光信号可以在实体瘤中迅速恢复。
总之，二硫键二氰染料为具有改善 T/B 值的特异性肿瘤激活荧光成像提供了一个有前途的平台。
