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Dual-channel fluorescence diagnosis of cancer cells/tissues assisted by OATP transporters and cysteine/glutathione†‡
Chemical Science ( IF 8.4 ) Pub Date : 2018-02-16 00:00:00 , DOI: 10.1039/c7sc05407f
Hongxing Zhang 1, 2, 3, 4 , Jing Liu 1, 2, 3, 4 , Bo Hu 3, 4, 5 , Linfang Wang 1, 2, 3, 4 , Zhen Yang 1, 2, 3, 4 , Xu Han 1, 2, 3, 4 , Juanjuan Wang 2, 3, 4, 6 , Wei Bai 4, 7, 8 , Wei Guo 1, 2, 3, 4
Affiliation  

Although fluorescence imaging diagnosis of the differences between cancer cells and normal cells by targeting ligand-based fluorescent probes is useful for recommending personalized therapy to patients, using the differences to diagnose a wide range of cancers is often not possible due to the genetic or phenotypic heterogeneity of cancer cells. In this work a 2-(diphenylphosphino)phenol-functionalized pyronin POP was presented as a dual-channel fluorescence agent for diagnosing a wide range of cancer cell types. The agent could efficiently penetrate cancer cell, rather than normal cell, membranes by active transport of the organic-anion transporting polypeptide (OATP) transporters overexpressed in many types of cancer cell, and is then activated by intracellular cysteine (Cys) and glutathione (GSH) to produce green-emission aminopyronin NP and red-emission thiopyronin SP, thereby enabling its use in dual-channel fluorescence diagnosis of a wide range of cancer cells with excellent contrast. Crucially, POP also displays the ability of dual-channel fluorescence diagnosis of cancer tissues from tumour xenograft models of mice and harvested surgical specimens of patients, thus holding great potential for clinical applications.

中文翻译:

OATP转运蛋白和半胱氨酸/谷胱甘肽辅助对癌细胞/组织的双通道荧光诊断

尽管通过靶向基于配体的荧光探针对癌细胞和正常细胞之间的差异进行荧光成像诊断有助于向患者推荐个性化治疗,但是由于遗传或表型异质性,通常无法使用差异来诊断广泛的癌症癌细胞。在这项工作中2-(二苯基膦基)苯酚官能化的pyronin POP作为一种双通道荧光剂,可用于诊断多种癌细胞类型。通过主动转运在许多类型的癌细胞中过表达的有机阴离子转运多肽(OATP)转运蛋白,该药物可以有效穿透癌细胞膜,而不是正常细胞膜,然后被细胞内半胱氨酸(Cys)和谷胱甘肽(GSH)激活)产生绿色发光的氨基吡咯烷酮NP和红色发光的硫吡喃酮SP,从而使其可用于双通道荧光诊断,以优异的对比度对多种癌细胞进行诊断。至关重要的是,POP 还显示了从小鼠的肿瘤异种移植模型和患者的手术标本中获得的癌组织双通道荧光诊断的能力,因此具有巨大的临床应用潜力。
更新日期:2018-02-16
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