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

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 combinato...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019911/
https://www.ncbi.nlm.nih.gov/pubmed/35656140
http://dx.doi.org/10.1039/d1sc06889j
Descripción
Sumario: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.