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Activatable fluorescence nanoprobes with only one kind of nanomaterial that can act as both the energy donor and acceptor simultaneously are scarce, but highly desirable for biosensing and bioimaging. In the present study, we reveal the preparation of self-quenched gold nanoclusters as a simple fluorescent turn-on probe for imaging intracellular glutathione. The self-quenched gold nanoclusters are prepared via disulfide bond-induced aggregation of gold nanoclusters. Compared with monodisperse gold nanoclusters, the developed self-quenched gold nanoclusters exhibit weak emission at 735 nm with a 40-nm red shift and much lower quantum yield (0.69%). The prepared self-quenched gold nanoclusters also possess good sensitivity and selectivity for glutathione detection, and are applicable for fluorescent turn-on imaging of intracellular glutathione.


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Self-quenched gold nanoclusters for turn-on fluorescence imaging of intracellular glutathione

Show Author's information Cong Dai1Chengxiong Yang1Xiuping Yan1,2,3,4( )
College of ChemistryResearch Center for Analytical SciencesTianjin Key Laboratory of Molecular Recognition and BiosensingNankai UniversityTianjin300071China
State Key Laboratory of Food Science and TechnologyJiangnan UniversityWuxi214122China
Institute of Analytical Food SafetySchool of Food Science and TechnologyJiangnan UniversityWuxi214122China
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)94 Weijin RoadTianjin300071China

Abstract

Activatable fluorescence nanoprobes with only one kind of nanomaterial that can act as both the energy donor and acceptor simultaneously are scarce, but highly desirable for biosensing and bioimaging. In the present study, we reveal the preparation of self-quenched gold nanoclusters as a simple fluorescent turn-on probe for imaging intracellular glutathione. The self-quenched gold nanoclusters are prepared via disulfide bond-induced aggregation of gold nanoclusters. Compared with monodisperse gold nanoclusters, the developed self-quenched gold nanoclusters exhibit weak emission at 735 nm with a 40-nm red shift and much lower quantum yield (0.69%). The prepared self-quenched gold nanoclusters also possess good sensitivity and selectivity for glutathione detection, and are applicable for fluorescent turn-on imaging of intracellular glutathione.

Keywords: imaging, gold nanoclusters, self-quenching, intracellular glutathione

References(53)

1

Jun, M. E.; Roy, B.; Ahn, K. H. "Turn-on" fluorescent sensing with "reactive" probes. Chem. Commun. 2011, 47, 7583–7601.

2

Kim, T.; Huh, Y. M.; Haam, S.; Lee, K. Activatable nanomaterials at the forefront of biomedical sciences. J. Mater. Chem. 2010, 20, 8194–8206.

3

Kobayashi, H.; Ogawa, M.; Alford, R.; Choyke, P. L.; Urano, Y. New strategies for fluorescent probe design in medical diagnostic imaging. Chem. Rev. 2010, 110, 2620–2640.

4

Wu, P.; Zhao, T.; Zhang, J. Y.; Wu, L.; Hou, X. D. Analyte-activable probe for protease based on cytochrome C-capped Mn: Zns quantum dots. Anal. Chem. 2014, 86, 10078–10083.

5

Yan, X.; Song, Y.; Zhu, C. Z.; Song, J. H.; Du, D.; Su, X. G.; Lin, Y. H. Graphene quantum dot-MnO2 nanosheet based optical sensing platform: A sensitive fluorescence "turn off-on" nanosensor for glutathione detection and intracellular imaging. ACS Appl. Mater. Interfaces 2016, 8, 21990–21996.

6

Wang, Q.; Zhang, S. R.; Zhong, Y. G.; Yang, X. F.; Li, Z.; Li, H. Preparation of yellow-green-emissive carbon dots and their application in constructing a fluorescent turn-on nanoprobe for imaging of selenol in living cells. Anal. Chem. 2017, 89, 1734–1741.

7

Gao, N.; Yang, W.; Nie, H. L.; Gong, Y. Q.; Jing, J.; Gao, L. J.; Zhang, X. L. Turn-on theranostic fluorescent nanoprobe by electrostatic self-assembly of carbon dots with doxorubicin for targeted cancer cell imaging, in vivo hyaluronidase analysis, and targeted drug delivery. Biosens. Bioelectron. 2017, 96, 300–307.

8

Peng, J. J.; Xu, W.; Teoh, C. L.; Han, S. Y.; Kim, B.; Samanta, A.; Er, J. C.; Wang, L.; Yuan, L.; Liu, X. G. et al. High-efficiency in vitro and in vivo detection of Zn2+ by dye-assembled upconversion nanoparticles. J. Am. Chem. Soc. 2015, 137, 2336–2342.

9

Li, N.; Li, Y. H.; Han, Y. Y.; Pan, W.; Zhang, T. T.; Tang, B. A highly selective and instantaneous nanoprobe for detection and imaging of ascorbic acid in living cells and in vivo. Anal. Chem. 2014, 86, 3924–3930.

10

Wu, B. Y.; Wang, H. F.; Chen, J. T.; Yan, X. P. Fluorescence resonance energy transfer inhibition assay for α-fetoprotein excreted during cancer cell growth using functionalized persistent luminescence nanoparticles. J. Am. Chem. Soc. 2011, 133, 686–688.

11

Zhou, Y.; Zhou, T. S.; Zhang, M.; Shi, G. Y. A DNA-scaffolded silver nanocluster/Cu2+ ensemble as a turn-on fluorescent probe for histidine. Analyst 2014, 139, 3122–3126.

12

Wang, Y.; Chen, J. T.; Yan, X. P. Fabrication of transferrin functionalized gold nanoclusters/graphene oxide nanocomposite for turn-on near-infrared fluorescent bioimaging of cancer cells and small animals. Anal. Chem. 2013, 85, 2529–2535.

13

Qin, L.; He, X. W.; Chen, L. X.; Zhang, Y. K. Turn-on fluorescent sensing of glutathione S-transferase at near-infrared region based on fret between gold nanoclusters and gold nanorods. ACS Appl. Mater. Interfaces 2015, 7, 5965–5971.

14

Meng, H. M.; Zhang, X. B.; Yang, C.; Kuai, H. L.; Mao, G. J.; Gong, L.; Zhang, W. H.; Feng, S. L.; Chang, J. B. Efficient two-photon fluorescence nanoprobe for turn-on detection and imaging of ascorbic acid in living cells and tissues. Anal. Chem. 2016, 88, 6057–6063.

15

Zhao, X.; Yang, C. X.; Chen, L. G.; Yan, X. P. Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumor-targeting and fluorescence-guided photothermal therapy. Nat. Commun. 2017, 8, 14998.

16

Jiang, H.; Xu, G.; Sun, Y. M.; Zheng, W. W.; Zhu, X. X.; Wang, B. J.; Zhang, X. J.; Wang, G. F. A "turn-on" silver nanocluster based fluorescent sensor for folate receptor detection and cancer cell imaging under visual analysis. Chem. Commun. 2015, 51, 11810–11813.

17

Hu, Y.; Heo, C. H.; Kim, G.; Jun, E. J.; Yin, J.; Kim, H. M.; Yoon, J. One-photon and two-photon sensing of biothiols using a bispyrene-Cu(Ⅱ) ensemble and its application to image GSH in the cells and tissues. Anal. Chem. 2015, 87, 3308–3313.

18

Li, Y. R.; Liu, Q.; Hong, Z. Y.; Wang, H. F. Magnetic separation-assistant fluorescence resonance energy transfer inhibition for highly sensitive probing of nucleolin. Anal. Chem. 2015, 87, 12183–12189.

19

Zhu, X. H.; Zhao, T. B.; Nie, Z.; Miao, Z.; Liu, Y.; Yao, S. Z. Nitrogen-doped carbon nanoparticle modulated turn-on fluorescent probes for histidine detection and its imaging in living cells. Nanoscale 2016, 8, 2205–2211.

20

Zhuang, Y.; Huang, F. J.; Xu, Q.; Zhang, M. S.; Lou, X. D.; Xia, F. Facile, fast-responsive, and photostable imaging of telomerase activity in living cells with a fluorescence turn-on manner. Anal. Chem. 2016, 88, 3289–3294.

21

Shi, W.; Ma, H. M. Rhodamine B thiolactone: A simple chemosensor for Hg2+ in aqueous media. Chem. Commun. 2008, 1856–1858.

22

Zhou, J.; Ma, H. M. Design principles of spectroscopic probes for biological applications. Chem. Sci. 2016, 7, 6309–6315.

23

Lu, Y. Z.; Chen, W. Sub-nanometre sized metal clusters: From synthetic challenges to the unique property discoveries. Chem. Soc. Rev. 2012, 41, 3594–3623.

24

Tao, Y.; Li, M. Q.; Ren, J. S.; Qu, X. G. Metal nanoclusters: Novel probes for diagnostic and therapeutic applications. Chem. Soc. Rev. 2015, 44, 8636–8663.

25

Zhang, L. B.; Wang, E. K. Metal nanoclusters: New fluorescent probes for sensors and bioimaging. Nanotoday 2014, 9, 132–157.

26

Shamsipur, M.; Molaabasi, F.; Hosseinkhani, S.; Rahmati, F. Detection of early stage apoptotic cells based on label-free cytochrome C assay using bioconjugated metal nanoclusters as fluorescent probes. Anal. Chem. 2016, 88, 2188–2197.

27

Dai, C.; Yang, C. X.; Yan, X. P. Ratiometric fluorescent detection of phosphate in aqueous solution based on near infrared fluorescent silver nanoclusters/metal-organic shell composite. Anal. Chem. 2015, 87, 11455–11459.

28

Yahia-Ammar, A.; Sierra, D.; Mérola, F.; Hildebrandt, N.; Le Guével, X. Self-assembled gold nanoclusters for bright fluorescence imaging and enhanced drug delivery. ACS Nano 2016, 10, 2591–2599.

29

Goswami, N.; Lin, F. X.; Liu, Y. B.; Leong, D. T.; Xie, J. P. Highly luminescent thiolated gold nanoclusters impregnated in nanogel. Chem. Mater. 2016, 28, 4009–4016.

30

Cao, F. F.; Ju, E. G.; Liu, C. Q.; Li, W.; Zhang, Y.; Dong, K.; Liu, Z.; Ren, J. S.; Qu, X. G. Encapsulation of aggregated gold nanoclusters into metal-organic frameworks for real-time monitoring of drug release. Nanoscale 2017, 9, 4128–4134.

31

Zhang, N.; Si, Y. M.; Sun, Z. Z.; Chen, L. J.; Li, R.; Qiao, Y. C.; Wang, H. Rapid, selective, and ultrasensitive fluorimetric analysis of mercury and copper levels in blood using bimetallic gold-silver nanoclusters with "silver effect"-enhanced red fluorescence. Anal. Chem. 2014, 86, 11714–11721.

32

Xu, N.; Zhu, Q.; Kong, X. Y.; Meng, L. A sensitive detection of Cr(VI) in wide pH range using polyethyleneimine protected silver nanoclusters. Anal. Methods 2016, 8, 5684–5689.

33

Liang, S.; Kuang, Y. F.; Ma, F. F.; Chen, S.; Long, Y. F. A sensitive spectrofluorometric method for detection of berberine hydrochloride using Ag nanoclusters directed by natural fish sperm DNA. Biosens. Bioelectron. 2016, 85, 758–763.

34

Guo, Y. H.; Tong, X. Y.; Ji, L. Y.; Wang, Z. L.; Wang, H. Y.; Hu, J. M.; Pei, R. J. Visual detection of Ca2+ based on aggregation-induced emission of Au(I)-Cys complexes with superb selectivity. Chem. Commun. 2015, 51, 596–598.

35

Shu, T.; Su, L.; Wang, J. X.; Lu, X.; Liang, F.; Li, C. Z.; Zhang, X. J. Value of the debris of reduction sculpture: Thiol etching of Au nanoclusters for preparing water-soluble and aggregation-induced emission-active Au(I) complexes as phosphorescent copper ion sensor. Anal. Chem. 2016, 88, 6071–6077.

36

Yang, X. M.; Yang, L.; Dou, Y.; Zhu, S. S. Synthesis of highly fluorescent lysine-stabilized Au nanoclusters for sensitive and selective detection of Cu2+ ion. J. Mater. Chem. C 2013, 1, 6748–6751.

37

Lai, X. D.; Tan, L. S.; Deng, X. L.; Liu, J. B.; Li, A. Q.; Liu, J. Y.; Hu, J. Q. Coordinatively self-assembled luminescent gold nanoparticles: Fluorescence turn-on system for high-efficiency passive tumor imaging. ACS Appl. Mater Interfaces 2017, 9, 5118–5127.

38

Yin, J.; Kwon, Y.; Kim, D.; Lee, D.; Kim, G.; Hu, Y.; Ryu, J. H.; Yoon, J. Preparation of a cyanine-based fluorescent probe for highly selective detection of glutathione and its use in living cells and tissues of mice. Nat. Protoc. 2015, 10, 1742–1754.

39

Wang, Y. H.; Jiang, K.; Zhu, J. L.; Zhang, L.; Lin, H. W. A fret-based carbon dot-MnO2 nanosheet architecture for glutathione sensing in human whole blood samples. Chem. Commun. 2015, 51, 12748–12751.

40

He, L. W.; Xu, Q. Y.; Liu, Y.; Wei, H. P.; Tang, Y. H.; Lin, W. Y. Coumarin-based turn-on fluorescence probe for specific detection of glutathione over cysteine and homocysteine. ACS Appl. Mater. Interfaces 2015, 7, 12809–12813.

41

Schnelldorfer, T.; Gansauge, S.; Gansauge, F.; Schlosser, S.; Beger, H. G.; Nussler, A. K. Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells. Cancer 2000, 89, 1440–1447.

DOI
42

Huang, Z. Z.; Chen, C.; Zeng, Z.; Yang, H.; Oh, J.; Chen, L.; Lu, S. C. Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver regeneration. FASEB J 2001, 15, 19–21.

43

Sun, S. K.; Dong, L. X.; Cao, Y.; Sun, H. R.; Yan, X. P. Fabrication of multifunctional Gd2O3/Au hybrid nanoprobe via a one-step approach for near-infrared fluorescence and magnetic resonance multimodal imaging in vivo. Anal. Chem. 2013, 85, 8436–8441.

44

Xie, J. P.; Zheng, Y. G.; Ying, J. Y. Protein-directed synthesis of highly fluorescent gold nanoclusters. J. Am. Chem. Soc. 2009, 131, 888–889.

45

Adhikari, B.; Banerjee, A. Facile synthesis of water-soluble fluorescent silver nanoclusters and Hg sensing. Chem. Mater. 2010, 22, 4364–4371.

46

Kumar, S. M.; Swaminathan, K.; Clemens, D. L.; Dey, A. GSH protects against oxidative stress and toxicity in VL-17A cells exposed to high glucose. Eur. J. Nutr. 2015, 54, 223–234.

47

Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coordination Compounds; 6th ed. John Wiley & Sons: New York, 2009.

48

Zhao, P.; He, K. Y.; Han, Y. T.; Zhang, Z.; Yu, M. Z.; Wang, H. H.; Huang, Y.; Nie, Z.; Yao, S. Z. Near-infrared dual-emission quantum dots-gold nanoclusters nanohybrid via co-template synthesis for ratiometric fluorescent detection and bioimaging of ascorbic acid in vitro and in vivo. Anal. Chem. 2015, 87, 9998–10005.

49

Mizusawa, K.; Ishida, Y.; Takaoka, Y.; Miyagawa, M.; Tsukiji, S.; Hamachi, I. Disassembly-driven turn-on fluorescent nanoprobes for selective protein detection. J. Am. Chem. Soc. 2010, 132, 7291–7293.

50

Li, X.; Zhu, S. J.; Xu, B.; Ma, K.; Zhang, J. H.; Yang, B.; Tian, W. J. Self-assembled graphene quantum dots induced by cytochrome C: A novel biosensor for trypsin with remarkable fluorescence enhancement. Nanoscale 2013, 5, 7776–7779.

51

Ho, L. C.; Wu, W. C.; Chang, C. Y.; Hsieh, H. H.; Lee, C. H.; Chang, H. T. Aptamer-conjugated polymeric nanoparticles for the detection of cancer cells through "turn-on" retro-self-quenched fluorescence. Anal. Chem. 2015, 87, 4925–4932.

52

Santra, S.; Kaittanis, C.; Santiesteban, O. J.; Perez, J. M. Cell-specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy. J. Am. Chem. Soc. 2011, 133, 16680–16688.

53

Feng, D.; Song, Y. C.; Shi, W.; Li, X. H.; Ma, H. M. Distinguishing folate-receptor-positive cells from folate-receptor-negative cells using a fluorescence off-on nanoprobe. Anal. Chem. 2013, 85, 6530–6535.

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Publication history
Copyright
Acknowledgements

Publication history

Received: 04 September 2017
Revised: 27 September 2017
Accepted: 28 September 2017
Published: 12 May 2018
Issue date: May 2018

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany 2017

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (No. 21435001), the Fundamental Research Funds for Central Universities (No. JUSRP51714B), and the Open Funds of the State Key Laboratory of Electroanalytical Chemistry (No. SKLEAC201705).

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