Dual-channel fluorescence diagnosis of cancer cells/tissues assisted by OATP transporters and cysteine/glutathione.
Dual-channel fluorescence diagnosis of cancer cells/tissues assisted by OATP transporters and cysteine/glutathione.
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OATP转运蛋白和半胱氨酸/谷胱甘肽辅助的癌细胞/组织双通道荧光诊断
DOI：
10.1039/c7sc05407f
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发表时间：
2018-03-28
期刊：
影响因子：
8.4
通讯作者：
Guo W
中科院分区：
文献类型：
--
作者：
Zhang H;Liu J;Hu B;Wang L;Yang Z;Han X;Wang J;Bai W;Guo W
一种2-（二苯基膦基）苯酚功能化的派洛宁染料已被成功开发用于OATP转运蛋白和Cys/GSH辅助的癌细胞/组织的双通道荧光诊断。虽然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对于向患者推荐个性化治疗是有用的，但是由于癌细胞的遗传或表型异质性，使用差异来诊断广泛的癌症通常是不可能的。在这项工作中，2-（二苯基膦基）苯酚官能化的派洛宁POP作为双通道荧光试剂用于诊断广泛的癌细胞类型。该试剂可以通过在许多类型的癌细胞中过表达的有机阴离子转运多肽（OATP）转运蛋白的主动转运而有效地穿透癌细胞而不是正常细胞的膜，然后被细胞内半胱氨酸（Cys）和谷胱甘肽（GSH）激活以产生绿色发射的氨基吡洛宁NP和红色发射的硫代吡洛宁SP，从而使其能够以优异的对比度用于宽范围癌细胞的双通道荧光诊断。最重要的是，POP还显示出对来自小鼠肿瘤异种移植模型和患者手术标本的癌症组织进行双通道荧光诊断的能力，因此具有巨大的临床应用潜力。
A 2-(diphenylphosphino)phenol-functionalized pyronin dye has successfully been developed for dual-channel fluorescence diagnosis of cancer cells/tissues assisted by OATP transporters and Cys/GSH. 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.
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