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Highly selective and ratiometric fluorescent nanoprobe for the detection of cysteine and its application in test strips

Analytical and Bioanalytical Chemistry volume 410, pages 4875–4884 (2018)Cite this article

Abstract

Cysteine (Cys) is a bithiol that plays a vital role in many physiological processes. However, it is difficult to discriminate Cys from homocysteine (Hcy) and glutathione (GSH), due to their similar chemical structures and reactivity. Herein, we have developed a polymeric nanoprobe, nanoHFA, for ratiometric, highly selective, and sensitive detection of Cys based on 7-hydroxycoumarin-3-carboxylic acid (HC) and fluorescein isothiocyanate (FITC)-acrylate (FITC-A) group-functionalized lipopolymer DSPE-PEG. The probe nanoHFA showed a strong fluorescence emission peak centered at 450 nm attributed to HC and a weak fluorescence emission peak centered at 520 nm due to the photoinduced electron transfer (PET) process of FITC induced by acrylate group. In the presence of Cys, the fluorescence signal at 520 nm could be lit up and the ratio of F520nm/F450nm showed a good linear relationship in the range of 5–60 μM with a low detection limit of 0.37 μM. The probe also displayed excellent water solubility and high selectivity to Cys over other biothiols such as Hcy and GSH. Moreover, we further used probe nanoHFA to detect Cu2+ ions in the range of 100–550 nM with a detection limit of 77 nM. The nanoprobe was successfully applied for the quantitative detection of Cys in fetal bovine serum, and fluorescent strips were developed for facile and visual detection of Cys and Cu2+ ions.

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References

  1. Wood ZA, Schröder E, Harris JR, Poole LB. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci. 2003;28(1):32–40.

    Article  CAS  PubMed  Google Scholar 

  2. Reddie KG, Carroll KS. Expanding the functional diversity of proteins through cysteine oxidation. Curr Opin Chem Biol. 2008;12(6):746–54.

    Article  CAS  PubMed  Google Scholar 

  3. Weerapana E, Wang C, Simon GM, Richter F, Khare S, Dillon MB, et al. Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature. 2010;468(7325):790–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li Q, Guo Y, Shao S. A BODIPY based fluorescent chemosensor for Cu (II) ions and homocysteine/cysteine. Sens Actuators B Chem. 2012;171:872–7.

    Article  CAS  Google Scholar 

  5. Niu LY, Guan YS, Chen YZ, Wu LZ, Tung CH, Yang QZ. A turn-on fluorescent sensor for the discrimination of cystein from homocystein and glutathione. Chem Commun. 2013;49(13):1294–6.

    Article  CAS  Google Scholar 

  6. Chwatko G, Bald E. Determination of cysteine in human plasma by high-performance liquid chromatography and ultraviolet detection after pre-column derivatization with 2-chloro-1-methylpyridinium iodide. Talanta. 2000;52(3):509–15.

    Article  CAS  PubMed  Google Scholar 

  7. Guan X, Hoffman B, Dwivedi C, Matthees DP. A simultaneous liquid chromatography/mass spectrometric assay of glutathione, cysteine, homocysteine and their disulfides in biological samples. J Pharm Biomed. 2003;31(2):251–61.

    Article  CAS  Google Scholar 

  8. Tang X, Liu Y, Hou H, You T. Electrochemical determination of L-tryptophan, L-tyrosine and L-cysteine using electrospun carbon nanofibers modified electrode. Talanta. 2010;80(5):2182–6.

    Article  CAS  PubMed  Google Scholar 

  9. Chen X, Zhou Y, Peng X, Yoon J. Fluorescent and colorimetric probes for detection of thiols. Chem Soc Rev. 2010;39(6):2120–35.

    Article  CAS  PubMed  Google Scholar 

  10. Wang H, Zhou G, Gai H, Chen X. A fluorescein-based probe with high selectivity to cysteine over homocysteine and glutathione. Chem Commun. 2012;48(67):8341–3.

    Article  CAS  Google Scholar 

  11. Xiang HJ, Tham HP, Nguyen MD, Phua SZF, Lim WQ, Liu JG, et al. An aza-BODIPY based near-infrared fluorescent probe for sensitive discrimination of cysteine/homocysteine and glutathione in living cells. Chem Commun. 2017;53(37):5220–3.

    Article  CAS  Google Scholar 

  12. Yue Y, Huo F, Ning P, Zhang Y, Chao J, Meng X, et al. Dual-site fluorescent probe for visualizing the metabolism of Cys in living cells. J Am Chem Soc. 2017;139(8):3181–5.

    Article  CAS  PubMed  Google Scholar 

  13. Niu LY, Chen YZ, Zheng HR, Wu LZ, Tung CH, Yang QZ. Design strategies of fluorescent probes for selective detection among biothiols. Chem Soc Rev. 2015;44(17):6143–60.

    Article  CAS  PubMed  Google Scholar 

  14. Niu W, Guo L, Li Y, Shuang S, Dong C, Wong MS. Highly selective two-photon fluorescent probe for ratiometric sensing and imaging cysteine in mitochondria. Anal Chem. 2016;88(3):1908–14.

    Article  CAS  PubMed  Google Scholar 

  15. Yang X, Guo Y, Strongin RM. Conjugate addition/cyclization sequence enables selective and simultaneous fluorescence detection of cysteine and homocysteine. Angew Chem Int Ed. 2011;50(45):10690–3.

    Article  CAS  Google Scholar 

  16. Kwon H, Lee K, Kim HJ. Coumarin–malonitrile conjugate as a fluorescence turn-on probe for biothiols and its cellular expression. Chem Commun. 2011;47(6):1773–5.

    Article  CAS  Google Scholar 

  17. Liu Y, Lv X, Hou M, Shi Y, Guo W. Selective fluorescence detection of cysteine over homocysteine and glutathione based on a cysteine-triggered dual Michael addition/retro-aza-aldol cascade reaction. Anal Chem. 2015;87(22):11475–83.

    Article  CAS  PubMed  Google Scholar 

  18. Liu J, Sun YQ, Huo Y, Zhang H, Wang L, Zhang P, et al. Simultaneous fluorescence sensing of Cys and GSH from different emission channels. J Am Chem Soc. 2013;136(2):574–7.

    Article  CAS  PubMed  Google Scholar 

  19. Guo J, Yang S, Guo C, Zeng Q, Qing Z, Cao Z, et al. Molecular engineering of α-substituted acrylate ester template for efficient fluorescence probe of hydrogen polysulfides. Anal Chem. 2017;90(1):881–7.

    Article  CAS  PubMed  Google Scholar 

  20. Pang L, Zhou Y, Gao W, Zhang J, Song H, Wang X, et al. Curcumin-based fluorescent and colorimetric probe for detecting cysteine in living cells and zebrafish. Ind Eng Chem Res. 2017;56(27):7650–5.

    Article  CAS  Google Scholar 

  21. Chen C, Liu W, Xu C, Liu W. A colorimetric and fluorescent probe for detecting intracellular biothiols. Biosens Bioelectron. 2016;85:46–52.

    Article  CAS  PubMed  Google Scholar 

  22. Rani BK, John SA. A novel pyrene based fluorescent probe for selective detection of cysteine in presence of other bio-thiols in living cells. Biosens Bioelectron. 2016;83:237–42.

    Article  CAS  PubMed  Google Scholar 

  23. Wang J, Li B, Zhao W, Zhang X, Luo X, Corkins ME, et al. Two-photon near infrared fluorescent turn-on probe toward cysteine and its imaging applications. ACS Sensor. 2016;1(7):882–7.

    Article  CAS  Google Scholar 

  24. Fu ZH, Han X, Shao Y, Fang J, Zhang ZH, Wang YW, et al. Fluorescein-based chromogenic and ratiometric fluorescence probe for highly selective detection of cysteine and its application in bioimaging. Anal Chem. 2017;89(3):1937–44.

    Article  CAS  PubMed  Google Scholar 

  25. Gao B, Cui L, Pan Y, Zhang G, Zhou Y, Zhang C, et al. A highly selective ratiometric fluorescent probe for biothiol and imaging in live cells. RSC Adv. 2016;6(49):43028–33.

    Article  CAS  Google Scholar 

  26. Lim CS, Masanta G, Kim HJ, Han JH, Kim HM, Cho BR. Ratiometric detection of mitochondrial thiols with a two-photon fluorescent probe. J Am Chem Soc. 2011;133(29):11132–5.

    Article  CAS  PubMed  Google Scholar 

  27. Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol. 2011;6(12):815–23.

    Article  CAS  PubMed  Google Scholar 

  28. Bae Y, Fukushima S, Harada A, Kataoka K. Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change. Angew Chem Int Edit. 2003;42(38):4640–3.

    Article  CAS  Google Scholar 

  29. Lu L, Feng C, Xu J, Wang F, Yu H, Xu Z, et al. Hydrophobic-carbon-dot-based dual-emission micelle for ratiometric fluorescence biosensing and imaging of Cu2+ in liver cells. Biosens Bioelectron. 2017;92:101–8.

    Article  CAS  PubMed  Google Scholar 

  30. Pan L, Sun S, Zhang L, Jiang K, Lin H. Near-infrared emissive carbon dots for two-photon fluorescence bioimaging. Nanoscale. 2017;8(39):17350–6.

    Article  CAS  Google Scholar 

  31. Song J, Li S, Zhao C, Lu Y, Zhao D, Sun J, et al. A superhydrophilic cement-coated mesh: an acid, alkali, and organic reagent-free material for oil/water separation. Nanoscale. 2018;10:1920–9.

    Article  CAS  PubMed  Google Scholar 

  32. Erdal NB, Hakkarainen M. Construction of bioactive and reinforced bioresorbable nanocomposites by reduced nano-graphene oxide carbon dots. Biomacromolecules. 2018;19:1074–81.

    Article  CAS  PubMed  Google Scholar 

  33. Domaille DW, Zeng L, Chang CJ. Visualizing ascorbate-triggered release of labile copper within living cells using a ratiometric fluorescent sensor. J Am Chem Soc. 2010;132(4):1194–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Siluvai GS, Mayfield M, Nilges MJ, DeBeer George S, Blackburn NJ. Anatomy of a red copper center: spectroscopic identification and reactivity of the copper centers of Bacillus subtilis Sco and its Cys-to-Ala variants. J Am Chem Soc. 2010;132(14):5215–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang YQ, Zhao T, He XW, Li WY, Zhang YK. A novel core-satellite CdTe/Silica/Au NCs hybrid sphere as dual-emission ratiometric fluorescent probe for Cu2+. Biosens Bioelectron. 2014;51:40–6.

    Article  CAS  PubMed  Google Scholar 

  36. Jo S, Kim D, Son SH, Kim Y, Lee TS. Conjugated poly (fluorene-quinoxaline) for fluorescence imaging and chemical detection of nerve agents with its paper-based strip. ACS Appl Mater Inter. 2014;6(2):1330–6.

    Article  CAS  Google Scholar 

  37. You M, Lin M, Gong Y, Wang S, Li A, Ji L, et al. Household fluorescent lateral flow strip platform for sensitive and quantitative prognosis of heart failure using dual-color upconversion nanoparticles. ACS Nano. 2017;11(6):6261–70.

    Article  CAS  PubMed  Google Scholar 

  38. Yan X, Li H, Zheng W, Su X. Visual and fluorescent detection of tyrosinase activity by using a dual-emission ratiometric fluorescence probe. Anal Chem. 2015;87(17):8904–9.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was financially supported by the National Natural Science Foundation of China (21775046, 21675055, 21635003).

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Author notes

  1. Fengyang Wang and Yingying Zhu contributed equally to this work.

Authors and Affiliations

  1. School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China

    Fengyang Wang, Yingying Zhu, Jie Xu, Zhiai Xu & Wen Zhang

  2. College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan, 250014, China

    Guiying Cheng

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  1. Fengyang Wang
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  2. Yingying Zhu
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  3. Jie Xu
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  4. Zhiai Xu
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Correspondence to Zhiai Xu or Wen Zhang.

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Wang, F., Zhu, Y., Xu, J. et al. Highly selective and ratiometric fluorescent nanoprobe for the detection of cysteine and its application in test strips. Anal Bioanal Chem 410, 4875–4884 (2018). https://doi.org/10.1007/s00216-018-1128-1

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  • DOI: https://doi.org/10.1007/s00216-018-1128-1

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