Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo

Nature Communications
Daisuke AsanumaYasuteru Urano

Abstract

Fluorescence-guided diagnostics is one of the most promising approaches for facile detection of cancer in situ. Here we focus on β-galactosidase, which is overexpressed in primary ovarian cancers, as a molecular target for visualizing peritoneal metastases from ovarian cancers. As existing fluorescence probes are unsuitable, we have designed membrane-permeable HMRef-βGal, in which the optimized intramolecular spirocyclic function affords >1,400-fold fluorescence enhancement on activation. We confirm that HMRef-βGal sensitively detects intracellular β-galactosidase activity in several ovarian cancer lines. In vivo, this probe visualizes metastases as small as <1 mm in diameter in seven mouse models of disseminated human peritoneal ovarian cancer (SHIN3, SKOV3, OVK18, OVCAR3, OVCAR4, OVCAR5 and OVCAR8). Because of its high brightness, real-time detection of metastases with the naked eye is possible. Endoscopic fluorescence detection of metastases is also demonstrated. The results clearly indicate preclinical potential value of the probe for fluorescence-guided diagnosis of peritoneal metastases from ovarian cancers.

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Citations

Mar 25, 2016·Bioconjugate Chemistry·Hiroyuki MatsuzakiYasuteru Urano
Mar 29, 2016·The Journal of Clinical Investigation·Keisuke KitakazeKohji Itoh
Apr 22, 2016·Current Opinion in Chemical Biology·Mako Kamiya, Yasuteru Urano
Jan 25, 2017·Scientific Reports·Satoshi YamaguchiAkimitsu Okamoto
Mar 22, 2016·Chemical Communications : Chem Comm·Panfei XingShiguo Sun
Jun 20, 2017·Journal of the American Chemical Society·Beatriz Lozano-TorresFélix Sancenón
Jul 13, 2016·Angewandte Chemie·Tomohiro DouraYasuteru Urano
Jan 10, 2018·Frontiers in Oncology·Tadanobu NagayaHisataka Kobayashi
May 23, 2018·Angewandte Chemie·Samer GnaimDoron Shabat
Aug 25, 2018·Chemical Society Reviews·Hong-Wen LiuWeihong Tan
Sep 28, 2018·Chemical Communications : Chem Comm·Rui ZhuShoufa Han
Dec 7, 2018·Chemical Society Reviews·Junji ZhangHe Tian
Sep 22, 2017·Journal of Biomedical Optics·Wenxiang CongGe Wang
Apr 9, 2019·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Tsutomu Ishi-IYoshinori Hagiwara
Jul 20, 2019·Biomaterials Science·Bing LiRunhui Liu
Jul 5, 2019·Modern Rheumatology·Zhipeng SuYunsen Li
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Aug 24, 2019·Angewandte Chemie·Eszter Baráth, Esteban Mejía
Nov 21, 2019·EMBO Molecular Medicine·Marta Paez-RibesDaniel Muñoz-Espín
Nov 26, 2019·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Shodai HinoAtsushi Ikeda
Mar 23, 2018·Beilstein Journal of Organic Chemistry·Futa OgawaMasaaki Omote

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Methods Mentioned

BETA
protein assay
Fluorescence

Software Mentioned

Maestro

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