Development of a fluorescent probe library enabling efficient screening of tumour-imaging probes based on discovery of biomarker enzymatic activities

Yugo Kuriki, Takafusa Yoshioka, Mako Kamiya, Toru Komatsu, Hiroyuki Takamaru, Kyohhei Fujita, Hirohisa Iwaki, Aika Nanjo, Yuki Akagi, Kohei Takeshita, Haruaki Hino, Rumi Hino, Ryosuke Kojima, Tasuku Ueno, Kenjiro Hanaoka, Seiichiro Abe, Yutaka Saito, Jun Nakajima, Yasuteru Urano

Research output: Contribution to journalArticlepeer-review

Abstract

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 in vitro screening and/or direct imaging-based ex vivo 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.

Original languageEnglish
JournalChemical Science
DOIs
Publication statusAccepted/In press - 2022
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

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