Kuriki Yugo, Yoshioka Takafusa, Kamiya Mako, Komatsu Toru, Takamaru Hiroyuki, Fujita Kyohhei, Iwaki Hirohisa, Nanjo Aika, Akagi Yuki, Takeshita Kohei, Hino Haruaki, Hino Rumi, Kojima Ryosuke, Ueno Tasuku, Hanaoka Kenjiro, Abe Seiichiro, Saito Yutaka, Nakajima Jun, Urano Yasuteru
Graduate School of Pharmaceutical Sciences, The University of Tokyo 7-3-1, Hongo Bunkyo-ku Tokyo Japan.
Graduate School of Medicine, The University of Tokyo 7-3-1, Hongo Bunkyo-ku Tokyo Japan
Chem Sci. 2022 Mar 21;13(16):4474-4481. doi: 10.1039/d1sc06889j. eCollection 2022 Apr 20.
Fluorescent probes that can selectively detect tumour lesions have great potential for fluorescence imaging-guided surgery. Here, we established a library-based approach for efficient screening of probes for tumour-selective imaging based on discovery of biomarker enzymes. We constructed a combinatorial fluorescent probe library for aminopeptidases and proteases, which is composed of 380 probes with various substrate moieties. Using this probe library, we performed lysate-based screening and/or direct imaging-based screening of freshly resected clinical specimens from lung or gastric cancer patients, and found promising probes for tumour-selective visualization. Further, we identified two target enzymes as novel biomarker enzymes for discriminating between tumour and non-tumour tissues. This library-based approach is expected to be an efficient tool to develop tumour-imaging probes and to discover new biomarker enzyme activities for various tumours and other diseases.
能够选择性检测肿瘤病变的荧光探针在荧光成像引导手术中具有巨大潜力。在此，我们基于生物标志物酶的发现，建立了一种基于文库的方法，用于高效筛选肿瘤选择性成像探针。我们构建了一个针对氨肽酶和蛋白酶的组合荧光探针文库，该文库由380个具有不同底物部分的探针组成。利用这个探针文库，我们对肺癌或胃癌患者的新鲜切除临床标本进行了基于裂解物的筛选和/或基于直接成像的筛选，发现了有前景的肿瘤选择性可视化探针。此外，我们确定了两种靶酶作为区分肿瘤组织和非肿瘤组织的新型生物标志物酶。这种基于文库的方法有望成为开发肿瘤成像探针以及发现各种肿瘤和其他疾病新生物标志物酶活性的有效工具。
