Mitochondria-targeting near-infrared ratiometric fluorescent probe for selective imaging of cysteine in orthotopic lung cancer mice
Mitochondria-targeting near-infrared ratiometric fluorescent probe for selective imaging of cysteine in orthotopic lung cancer mice
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线粒体靶向近红外比率荧光探针用于原位肺癌小鼠半胱氨酸的选择性成像
DOI：
10.1016/j.snb.2018.11.056
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Chen Lingxin
中科院分区：
文献类型：
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作者：
Zhang Xiaoyu;He Na;Huang Yan;Yu Fabiao;Li Bowei;Lv Changjun;Chen Lingxin
半胱氨酸（Cys）在许多生理过程中起着重要作用，尽管其正常浓度维持在微摩尔水平。异常高水平的细胞内Cys可导致许多疾病，包括癌症。近年来，人们开发了许多有效的荧光探针，用于选择性检测Cys和其他生物硫醇。本文合成了一种用于细胞内半胱氨酸选择性成像的比率近红外荧光探针Cy-OAcr，Cy-OAcr具有亲脂性的亚胺阳离子单元作为线粒体导向单元和丙烯酸酯基团作为半胱氨酸识别单元，以及用于重排菁荧光团共轭π电子系统的荧光调节剂。在检测Cys时，发生显著的吸收和荧光光谱偏移，这对于比率检测是有利的。该探针对Cys的检测灵敏度和选择性高于谷胱甘肽（GSH）、同型半胱氨酸（Hcy）和其他生物分子，检测下限为0.09 μM。ProbeCy-OAcris能够在三种活癌细胞系及其相应的荷瘤小鼠模型中检测和成像Cys。更重要的是，我们成功地将这种荧光探针应用于原位肺癌模型中Cys水平的评估。成像分析表明，该探针可以区分肿瘤病变和正常组织，表明其在临床癌症辅助诊断方面具有重要的潜在应用价值。
Cysteine (Cys) plays significant roles in many physiological processes, although its normal concentration is maintained at the micromole level. Abnormally high levels of intracellular Cys can lead to many diseases including cancer. Recent years, many effective fluorescent probes have been developed for the selective detection of Cys against other biological thiols. Herein, we synthesized a ratiometric near-infrared (NIR) fluorescent probeCy-OAcrfor selective imaging of intracellular Cys.Cy-OAcrhas a lipophilic iminium cation unit as the mitochondrial guider and an acrylate group as the Cys recognition unit as well as a fluorescence modulator for rearranging the conjugated π-electron system of cyanine fluorophore. Upon detection of Cys, there occurs a significant absorption and fluorescence spectral shift, which are desirably beneficial for ratiometric detection. This probe has high sensitivity and selectivity for Cys detection over glutathione (GSH), homocysteine (Hcy), and other biomolecules with a low limit of detection at 0.09 μM. ProbeCy-OAcris capable to detect and image Cys in three living cancer cell lines and their corresponding tumor-bearing mice models. More importantly, we successfully apply this fluorescent probe to evaluate the level of Cys in orthotopic lung cancer model. Imaging analyses reveal that the probe can discriminate tumor lesions from normal tissues, indicating its significant potential applications for clinical auxiliary diagnosis of cancer.