ChemComm
COMMUNICATION
DOI: 10.1039/C4C 7656G
JournC0al Name
Importantly, the fluorescence of T2 in brain sections also could be 5. M. Royzen, A. Durandin, V. G. Young, N. E. Geacintov and J. W.
tuned by varying the irradiation wavelength. Microꢀfluorescence Canary, J. Am. Chem. Soc., 2006, 128, 3854.
switching in brain sections was achieved by alternating between UV 6. J. Rosenthal and S. J. Lippard, J. Am. Chem. Soc., 2010, 132, 5536.
and visible light illumination. The selected T2ꢀstained Aβ deposits 7. V. Amendola, G. Bergamaschi, M. Boiocchi, L. Fabbrizzi and L.
(circular region in Fig. 3D) were irradiated with 405 nm light for 150 s,
Mosca, J. Am. Chem. Soc., 2013, 135, 6345.
and the fluorescence of the irradiated deposits was turned off, due to T2 8. D. J. Selkoe, Ann. N. Y. Acad. Sci., 2000, 924, 17ꢀ25.
in this area changing from an open state to a closed state. Interestingly, 9. W. Annaert and B. De Strooper, Annu. Rev. Cell Dev. Biol., 2002, 18
,
the fluorescence of the Aβ deposits could be recovered by 633 nm light
25.
irradiation from the CLSM lamp for 10 min (Fig. 3D). The fluorescence 10. L. Cai, R. B. Innis and V. W. Pike, Curr. Med. Chem., 2007, 14, 19.
intensity of T2 showed reversible changes with alternating irradiation 11. H. Quigley, S. J. Colloby and J. T. O'Brien, Int J Geriatr Psychiatry
,
of UV and visible light, validating the photochromic properties of T2
and indicating that the probes show remarkable antiꢀphotobleaching in 12. C. C. Rowe and V. L. Villemagne, J. Nucl. Med., 2011, 52, 1733.
tissues. As evident in Fig. S16, the optical switching of fluorescence 13. C. A. Mathis, N. S. Mason, B. J. Lopresti and W. E. Klunk, Semin
can be repeated many times with little “fatigue” effects or Nucl Med, 2012, 42, 423.
photobleaching, that were thought to be fatal disadvantages of the 14. Y. O. Lee, J. W. Shin, C. Yi, Y. H. Lee, N. W. Sohn, C. Kang and J.
general fluorophore. As a contrast, ThT (a common standard stain for S. Kim, Chem Commun, 2014, 50, 5741.
Aβ plaques) stained brain sections were also irradiated with UV and 15. K. Liu, T. L. Guo, J. Chojnacki, H.ꢀG. Lee, X. Wang, S. L. Siedlak,
visible light. The fluorescence intensity of ThT was rapidly quenched W. Rao, X. Zhu and S. Zhang, ACS Chem. Neurosci., 2012, , 141.
by UV light and did not recover under visible light (Fig. 3E). In 16. A. Aaslund, C. J. Sigurdson, T. Klingstedt, S. Grathwohl, T.
2011, 26, 991.
3
addition, both T1 and T2 show low cytotoxicity by means of an MTT
assay. The cellular viabilities were estimated to be greater than 85%
after 2 h in the presence of 1–100 ꢁM T1 or T2 (Fig. S17). Thus, we
concluded that T2 is a novel and superior fluorescence dye for use as a
marker of Aβ deposits.
Bolmont, D. L. Dickstein, E. Glimsdal, S. Prokop, M. Lindgren, P.
Konradsson, D. M. Holtzman, P. R. Hof, F. L. Heppner, S. Gandy,
M. Jucker, A. Aguzzi, P. Hammarstroem and K. P. R. Nilsson, ACS
Chem. Biol., 2009, 4, 673.
17. E. E. Nesterov, J. Skoch, B. T. Hyman, W. E. Klunk, B. J. Bacskai
In summary, we designed and synthesized diaryletheneꢀbased
and T. M. Swager, Angew. Chem., Int. Ed., 2005, 44, 5452.
fluorescent probes capable of specifically detecting Aβ aggregates. The 18. K. Cao, M. Farahi, M. Dakanali, W. M. Chang, C. J. Sigurdson, E. A.
fluorescent intensity dramatically increased in the presence of Aβ Theodorakis and J. Yang, J. Am. Chem. Soc., 2012, 134, 17338.
aggregates, accompanied with a blue shift. The fluorescence can be 19. X. Zhang, Y. Tian, Z. Li, X. Tian, H. Sun, H. Liu, A. Moore and C.
readily tuned under alternating irradiating with UV and visible light, Ran, J. Am. Chem. Soc., 2013, 135, 16397.
exhibiting excellent fatigue resistance and antiꢀphotobleaching. These 20. L. Zhu, W. Wu, M.ꢀQ. Zhu, J. J. Han, J. K. Hurst and A. D. Q. Li, J.
probes can specifically target Aβ deposits in brain sections. The Am. Chem. Soc., 2007, 129, 3524.
synergistic binding effect of DAE and ANCA to the hydrophobic 21. M. Irie, Chem. Rev., 2000, 100, 1683.
pockets of Aβ aggregates contribute to the binding efficiency of the 22. W. Li, C. Jiao, X. Li, Y. Xie, K. Nakatani, H. Tian and W. Zhu,
probes. The switchable fluorescence image operated by light in brain
tissues may provide a new window for in vivo high resolution imaging. 23. Y. Zou, T. Yi, S. Xiao, F. Li, C. Li, X. Gao, J. Wu, M. Yu and C.
Further studies of these probes are ongoing in our laboratory. Huang, J. Am. Chem. Soc., 2008, 130, 15750.
The authors thanks for the financially support by 973 24. M. Bates, B. Huang, G. T. Dempsey and X. Zhuang, Science, 2007,
Angew. Chem., Int. Ed., 2014, 53, 4603.
(2013CB733700), NNSFC (21125104, 51373039), PIRTU (IRT1117)
317, 1749ꢀ1753
and Shanghai Sci. Tech. Comm. (12XD1405900).
25. N. Soh, K. Yoshida, H. Nakajima, K. Nakano, T. Imato, T.
Fukaminato and M. Irie, Chem. Commun., 2007, 5206.
26. U. AlꢀAtar, R. Fernandes, B. Johnsen, D. Baillie and N. R. Branda, J.
Am. Chem. Soc., 2009, 131, 15966.
Notes and references
a
Department of Chemistry & Innovation Center of Chemistry for Energy
Materials, Fudan University, 220 Handan Road, Shanghai 200433, P. R. 27. K. Liu, Y. Wen, T. Shi, Y. Li, F. Li, Y. L. Zhao, C. Huang and T. Yi,
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b
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Institute of Health Sciences, 263 South Jiefang Road, Yancheng 224005,
Jiangsu, P. R. China. Eꢀmail anyangsun@hotmail.com.
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