A Two-Photon Fluorescent Probe for Specific Imaging of Furin Activity in Living Cells and Tissues

doi:10.6023/A20070323

Acta Chimica Sinica ›› 2020, Vol. 78 ›› Issue (11): 1240-1245.DOI: 10.6023/A20070323 Previous Articles Next Articles

Article

用于细胞和组织中弗林蛋白酶特异性成像的双光子荧光探针研究

刘红文, 朱隆民, 娄霄峰, 袁林, 张晓兵

湖南大学化学化工学院化学/生物传感与计量学国家重点实验室分子科学与生物医学实验室长沙 410082

投稿日期:2020-07-22 发布日期:2020-07-28
通讯作者: 张晓兵 E-mail:xbzhang@hnu.edu.cn
基金资助:
项目受国家自然科学基金（Nos.21890744，21877029）、国家重点研发计划（No.2019YFA0210103）和国家博士后创新人才计划（No.BX20180093）资助.

A Two-Photon Fluorescent Probe for Specific Imaging of Furin Activity in Living Cells and Tissues

Liu Hongwen, Zhu Longmin, Lou Xiaofeng, Yuan Lin, Zhang Xiao-Bing

Molecular Science and Biomedicine Laboratory(MBL), College of Chemistry and Chemical Engineering, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha 410082, China

Received:2020-07-22 Published:2020-07-28
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21890744 and 21877029), National Key R&D Program of China (No. 2019YFA0210103), and the National Postdoctoral Program for Innovative Talents (No. BX20180093).

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Abstract

Furin, the most characteristic member of the proprotein convertase (PCs), has important biological functions. The expression level of furin is related to many diseases, for example, the occurrence and development of cancer is closely related to the expression level of furin. Although several small-molecule fluorescent probes for furin have been developed, which were designed based on near-infrared dye or one-photon dye. These probes exhibit low Stocks' shift or shallow penetration depth, which leading to self-quenching and strong interference. Two-photon fluorescent probes, which utilize two near-infrared photons as the excitation source, can overcome these problems. Herein, a furin-activatable two-photon fluorescent probe (Nap-F) was developed firstly that allowed for detection and imaging of furin in live cells and tumor tissues. Nap-F consists of a classical two-photon fluorophore (1,8-naphthalimide), a furin-particular polypeptide sequence RVRR and a self-eliminating linker. Nap-F is water-soluble and in a fluorescence-off state itself due to the inhibited intramolecular charge transfer (ICT). In the absence of furin, no noticeable fluorescence enhancement was detected, even over 3 days in buffer solution, indicating its good stability. Upon the conversion by furin, it displayed a dramatically fluorescence enhancement at 545 nm, and exhibits high specificity and sensitivity to furin. Nap-F was applied for visualizing the difference in the expression level of furin in various cells, demonstrating its capacity of distinguishing some cancer cells from normal cells. Furthermore, Nap-F was utilized to visualize the variation of furin expression level efficiently after immobilization of hypoxia-inducible factor-1 (HIF-1) by CoCl₂, with the results indicating that there is a positive correlation between the expression level of furin and the degree of hypoxia in tumor cells. Owing to the excellent property of Nap-F, the probe was also successful utilized to imaging furin activity in tumor tissues. Thus, Nap-F is able to serve as a potential tool for better exploring the intrinsic link between hypoxic physiological environment and cellular carcinogenesis and detecting cancer in preclinical applications.

Key words: two-photon, fluorescent probe, furin, cancer, hypoxia

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Liu Hongwen, Zhu Longmin, Lou Xiaofeng, Yuan Lin, Zhang Xiao-Bing. A Two-Photon Fluorescent Probe for Specific Imaging of Furin Activity in Living Cells and Tissues[J]. Acta Chimica Sinica, 2020, 78(11): 1240-1245.

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用于细胞和组织中弗林蛋白酶特异性成像的双光子荧光探针研究

A Two-Photon Fluorescent Probe for Specific Imaging of Furin Activity in Living Cells and Tissues

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