Yogo Takao, Umezawa Keitaro, Kamiya Mako, Hino Rumi, Urano Yasuteru
PRESTO, Japan Science and Technology Agency , 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
Department of Sports and Health Science, Daito Bunka University , 560 Iwadono, Higashimathuyama, Saitama 355-8501, Japan.
Bioconjug Chem. 2017 Aug 16;28(8):2069-2076. doi: 10.1021/acs.bioconjchem.7b00233. Epub 2017 Jul 26.
Technology to visualize small prostate cancers is urgently needed because of the difficulty of discriminating prostate cancer from normal tissue with the naked eye, and a fluorescence imaging method would be advantageous. Here, we describe the design and synthesis of a fluorogenic probe (Ac-KQLR-HMRG) that is activated by hepsin and matriptase (proteases over-expressed in prostate cancer). Ac-KQLR-HMRG exhibited significant turn-on fluorogenicity in the presence of hepsin (180-fold) and matriptase (80-fold) and allowed specific fluorescence imaging of various prostate cancer cell line in vitro. In addition, the probe enabled rapid imaging (within 1-10 min) of small prostate cancer nodules in mouse models of disseminated peritoneal tumor and orthotopic tumor.
由于肉眼难以区分前列腺癌与正常组织，因此迫切需要能够可视化小前列腺癌的技术，而荧光成像方法将具有优势。在此，我们描述了一种荧光探针（Ac-KQLR-HMRG）的设计与合成，该探针可被hepsin和matriptase（在前列腺癌中过表达的蛋白酶）激活。Ac-KQLR-HMRG在hepsin（180倍）和matriptase（80倍）存在的情况下表现出显著的开启荧光性，并能够在体外对各种前列腺癌细胞系进行特异性荧光成像。此外，该探针能够在播散性腹膜肿瘤和原位肿瘤小鼠模型中对小前列腺癌结节进行快速成像（1 - 10分钟内）。
