Citation: 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. doi: 10.6023/A20070323 shu

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

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

Corresponding author: Zhang Xiao-Bing, xbzhang@hnu.edu.cn
Received Date: 22 July 2020
Available Online: 27 July 2020
Fund Project: the National Natural Science Foundation of China 21890744National Key R & D Program of China 2019YFA0210103the National Postdoctoral Program for Innovative Talents BX20180093Project 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)the National Natural Science Foundation of China 21877029

Figures(5)

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.
- two-photon,
- fluorescent probe,
- furin,
- cancer,
- hypoxia
1. [1]
  Steiner, D. F. Curr. Opin. Chem. Biol. 1998, 2, 31. doi: 10.1016/S1367-5931(98)80033-1
2. [2]
  Seidah, N. G.; Mayer, G.; Zaid, A.; Rousselet, E.; Nassoury, N.; Poirier, S.; Essalmani, R.; Prat, A. Int. J. Biochem. Cell Biol. 2008, 40, 1111. doi: 10.1016/j.biocel.2008.01.030
3. [3]
  Bassi, D. E.; Fu, J.; de Cicco, R. L.; Klein-Szanto, A. J. P. Mol. Carcinogen 2005, 44, 151. doi: 10.1002/mc.20134
4. [4]
  McMahon, S.; Grondin, F.; McDonal, P. P.; Richard, D. E.; Dubois, C. M. J. Biol. Chem. 2005, 280, 6561. doi: 10.1074/jbc.M413248200
5. [5]
  Zhang, J.; Liu, H.-W.; Hu, X.-X.; Li, J.; Liang, L.-H.; Zhang, X.-B.; Tan, W. Anal. Chem. 2015, 87, 11832. doi: 10.1021/acs.analchem.5b03336
6. [6]
  Li, X.; Gao, X.; Shi, W.; Ma, H. Chem. Rev. 2014, 114, 590. doi: 10.1021/cr300508p
7. [7]
  Yang, L.; Liu, B.; Li, N.; Tang, B. Acta Chim. Sinica, 2017, 75, 1047. (in Chinese).
8. [8]
  Yang, Z.; He, Y.; Dai, B.; Dou, B.; Wang, J.; Peng, X. Acta Chim. Sinica, 2011, 69, 445(in Chinese).
9. [9]
  Guan, X.; Wang, L.; Li, Z.; Liu, M.; Wang, K.; Lin, B.; Yang, X.; Lai, S.; Lei, Z.. Acta Chim. Sinica, 2019, 77, 1036(in Chinese).
10. [10]
  Hou, J.; Li, K.; Qin, C. Yu, X.; Chin. J. Org. Chem. 2018, 38, 612(in Chinese).
11. [11]
  Liu, H.-W.; Chen, L.; Xu, C.; Li, Z.; Zhang, H.; Zhang, X.-B.; Tan, W. Chem. Soc. Rev. 2018, 47, 7140. doi: 10.1039/C7CS00862G
12. [12]
  Zhu, L.; Liu, H.-W.; Yang, Y.; Hu, X.-X.; Li, K.; Xu, S.; Li, J.-B.; Ke, G.; Zhang, X.-B. Anal. Chem. 2019, 91, 9682. doi: 10.1021/acs.analchem.9b01220
13. [13]
  Li, K.; Hu, X.-X.; Liu, H.-W.; Xu, S.; Huan, S.-Y.; Li, J.-B.; Deng, T.-G.; Zhang, X.-B. Anal. Chem. 2018, 90, 11680. doi: 10.1021/acs.analchem.8b03335
14. [14]
  Zhao, X.; Lv, G.; Peng, Y.; Liu, Q.; Li, X.; Wang, S.; Li, K.; Qiu, L.; Lin, J. ChemBioChem 2018, 19, 1060. doi: 10.1002/cbic.201800015
15. [15]
  Mu, J.; Liu, F.; Rajab, M. S.; Shi, M.; Li, S.; Goh, C.; Lu, L.; Xu, Q.-H.; Liu, B.; Ng, L. G., Xing B. Angew. Chem. Int. Ed. 2014, 53, 14357. doi: 10.1002/anie.201407182
16. [16]
  Liu, X.; Liang, G. Chem. Commun. 2017, 53, 1037. doi: 10.1039/C6CC09106G
17. [17]
  Liu, H.-W.; Liu, Y.; Wang, P.; Zhang, X.-B. Methods Appl. Fluoresc. 2017, 5, 012003. doi: 10.1088/2050-6120/aa61b0
18. [18]
  Kim, H.; Cho, B. Chem. Rev. 2015, 115, 5014. doi: 10.1021/cr5004425
19. [19]
  Kim, H.; Cho, B. Acc. Chem. Res. 2009, 42, 863. doi: 10.1021/ar800185u
20. [20]
  Liu, H.-W.; Zhang, X.-B.; Zhang, J.; Wang, Q.-Q.; Hu, X.-X.; Wang, P.; Tan, W. Anal. Chem. 2015, 87, 8896. doi: 10.1021/acs.analchem.5b02021
21. [21]
  Huang, C.; Chen, H.; Li, F. An, S. Chin. J. Org. Chem. 2019, 39, 2467(in Chinese).
22. [22]
  Dragulescu-Andrasi, A.; Kothapalli, S.-R.; Tikhomirov, G. A.; Rao, J.; Gambhir, S. S. J. Am. Chem. Soc. 2013, 135, 11015. doi: 10.1021/ja4010078
23. [23]
  Yuan, Y.; Zhang, J.; Cao, Q.; An, L.; Liang, G. Anal. Chem. 2015, 87, 6180. doi: 10.1021/acs.analchem.5b01656
24. [24]
  Xu, S.; Liu, H.-W.; Hu, X.-X.; Huan, S.-Y.; Zhang, J.; Liu, Y.-C.; Yuan, L.; Qu, F.-L.; Zhang, X.-B.; Tan, W. Anal. Chem. 2017, 89, 7641. doi: 10.1021/acs.analchem.7b01561
25. [25]
  Thorn-Seshold, O.; Vargas-Sanchez, M.; McKeon, S.; Hasserodt, J. Chem. Commun. 2012, 48, 6253. doi: 10.1039/c2cc32227g
26. [26]
  Ou-Yang, J.; Li, Y.-F.; Wu, P.; Jiang, W.-L.; Liu, H.-W.; Li, C.-Y. ACS Sens. 2018, 3, 1354. doi: 10.1021/acssensors.8b00274
27. [27]
  Ma, J.; Evrard, S.; Badiola, I.; Siegfried, G.; Khatib, A. M. Eur. J. Cell Biol., 2017, 96, 457. doi: 10.1016/j.ejcb.2017.06.001
28. [28]
  Feng, L.; Li, P.; Hou, J.; Cui, Y.-L.; Tian, X.-G.; Yu, Z.-L.; Cui, J.-N.; Wang, C.; Huo, X.-K.; Ning, J., Ma X.-C. Anal. Chem. 2018, 90, 13341. doi: 10.1021/acs.analchem.8b02857
1. [1]
  Qi Wang , Yicong Gao , Feng Lu , Quli Fan . Preparation and Performance Characterization of the Second Near-Infrared Phototheranostic Probe: A New Design and Teaching Practice of Polymer Chemistry Comprehensive Experiment. University Chemistry, 2024, 39(11): 342-349. doi: 10.12461/PKU.DXHX202404141
2. [2]
  Jinlong YAN , Weina WU , Yuan WANG . A simple Schiff base probe for the fluorescent turn-on detection of hypochlorite and its biological imaging application. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1653-1660. doi: 10.11862/CJIC.20240154
3. [3]
  Meirong HAN , Xiaoyang WEI , Sisi FENG , Yuting BAI . A zinc-based metal-organic framework for fluorescence detection of trace Cu²⁺. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1603-1614. doi: 10.11862/CJIC.20240150
4. [4]
  Xin Lv , Hongxing Zhang , Kaibo Duan , Wenhui Dai , Zhihui Wen , Wei Guo , Junsheng Hao . Lighting the Way Against Cancer: Photodynamic Therapy. University Chemistry, 2024, 39(5): 70-79. doi: 10.3866/PKU.DXHX202309090
5. [5]
  Jiakun BAI , Ting XU , Lu ZHANG , Jiang PENG , Yuqiang LI , Junhui JIA . A red-emitting fluorescent probe with a large Stokes shift for selective detection of hypochlorous acid. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1095-1104. doi: 10.11862/CJIC.20240002
6. [6]
  Xinyi Hong , Tailing Xue , Zhou Xu , Enrong Xie , Mingkai Wu , Qingqing Wang , Lina Wu . Non-Site-Specific Fluorescent Labeling of Proteins as a Chemical Biology Experiment. University Chemistry, 2024, 39(4): 351-360. doi: 10.3866/PKU.DXHX202310010
7. [7]
  Yan ZHAO , Xiaokang JIANG , Zhonghui LI , Jiaxu WANG , Hengwei ZHOU , Hai GUO . Preparation and fluorescence properties of Eu³⁺-doped CaLaGaO₄ red-emitting phosphors. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1861-1868. doi: 10.11862/CJIC.20240242
8. [8]
  Xinyu Liu , Weiran Hu , Zhengkai Li , Wei Ji , Xiao Ni . Algin Lab: Surging Luminescent Sea. University Chemistry, 2024, 39(5): 396-404. doi: 10.3866/PKU.DXHX202312021
9. [9]
  Xuzhen Wang , Xinkui Wang , Dongxu Tian , Wei Liu . Enhancing the Comprehensive Quality and Innovation Abilities of Graduate Students through a “Student-Centered, Dual Integration and Dual Drive” Teaching Model: A Case Study in the Course of Chemical Reaction Kinetics. University Chemistry, 2024, 39(6): 160-165. doi: 10.3866/PKU.DXHX202401074
10. [10]
  Siyi ZHONG , Xiaowen LIN , Jiaxin LIU , Ruyi WANG , Tao LIANG , Zhengfeng DENG , Ao ZHONG , Cuiping HAN . Targeting imaging and detection of ovarian cancer cells based on fluorescent magnetic carbon dots. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1483-1490. doi: 10.11862/CJIC.20240093
11. [11]
  Chun-Lin Sun , Yaole Jiang , Yu Chen , Rongjing Guo , Yongwen Shen , Xinping Hui , Baoxin Zhang , Xiaobo Pan . Construction, Performance Testing, and Practical Applications of a Home-Made Open Fluorescence Spectrometer. University Chemistry, 2024, 39(5): 287-295. doi: 10.3866/PKU.DXHX202311096
12. [12]
  Jianjun Liu , Xue Yang , Chi Zhang , Xueyu Zhao , Zhiwei Zhang , Yongmei Chen , Qinghong Xu , Shao Jin . Preparation and Fluorescence Characterization of CdTe Semiconductor Quantum Dots. University Chemistry, 2024, 39(7): 307-315. doi: 10.3866/PKU.DXHX202311031
13. [13]
  Zishuo Yi , Peng Liu , Yan Xu . Fluorescent “Chameleon”: A Popular Science Experiment Based on Dynamic Luminescence. University Chemistry, 2024, 39(9): 304-310. doi: 10.12461/PKU.DXHX202311079
14. [14]
  Quanliang Chen , Zhaohui Zhou . Research on the Active Site of Nitrogenase over Fifty Years. University Chemistry, 2024, 39(7): 287-293. doi: 10.3866/PKU.DXHX202310133
15. [15]
  Lei Shu , Zhengqing Hao , Kai Yan , Hong Wang , Lihua Zhu , Fang Chen , Nan Wang . Development of a Double-Carbon Related Experiment: Preparation, Characterization and Carbon-Capture Ability of Eggshell-Derived CaO. University Chemistry, 2024, 39(4): 149-156. doi: 10.3866/PKU.DXHX202310134
16. [16]
  Jin Yan , Chengxia Tong , Yajie Li , Yue Gu , Xuejian Qu , Shigang Wei , Wanchun Zhu , Yupeng Guo . Construction of a “Dual Support, Triple Integration” Chemical Safety Practical Education System. University Chemistry, 2024, 39(7): 69-75. doi: 10.12461/PKU.DXHX202405008
17. [17]
  Linhan Tian , Changsheng Lu . Discussion on Sextuple Bonding in Diatomic Motifs of Chromium Family Elements. University Chemistry, 2024, 39(8): 395-402. doi: 10.3866/PKU.DXHX202401056
18. [18]
  Wei Gao , Jinyue Yang , Wenwei Zhang . Practice and Exploration of Promoting the “Double Reduction” Work with Popular Science Resources in Universities. University Chemistry, 2024, 39(9): 385-391. doi: 10.3866/PKU.DXHX202311008
19. [19]
  Peiran ZHAO , Yuqian LIU , Cheng HE , Chunying DUAN . A functionalized Eu³⁺ metal-organic framework for selective fluorescent detection of pyrene. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 713-724. doi: 10.11862/CJIC.20230355
20. [20]
  Lin Song , Dourong Wang , Biao Zhang . Innovative Experimental Design and Research on Preparing Flexible Perovskite Fluorescent Gels Using 3D Printing. University Chemistry, 2024, 39(7): 337-344. doi: 10.3866/PKU.DXHX202310107

Get Citation

PDF

XML

Metrics

PDF Downloads(9)
Abstract views(699)
HTML views(77)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142