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Potassium triiodide-quenched gold nanocluster as a fluorescent turn-on probe for sensing cysteine/homocysteine in human serum

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Abstract

A fluorescent sensing platform using KI3-quenched bovine serum albumin stabilized gold nanoclusters has been designed and used as a fluorescent probe for the turn-on detection of homocysteine/cysteine (Cys/Hcy). The fluorescence of gold nanoclusters was quenched by iodine. The fluorescence of quenched gold nanoclusters was effectively switched on by Cys/Hcy devoid of the interference of glutathione. The transmission electron microscopy image, X-ray photoelectron spectroscopy analysis, time-correlated single photon counting analysis, and dynamic light scattering data confirmed the aggregation-induced quenching of fluorescence of gold nanoclusters by iodine. The turn-on response of Cys/Hcy shows two linear ranges from 0.0057 to 5 μM and from 8 to 25 μM, with a limit of detection of 9 nM for cysteine and 12 nM for homocysteine. Real samples were analyzed to monitor Cys/Hcy added to human serum. The fluorescence turn-on response of the probe on a paper strip in the presence of Cys/Hcy was studied.

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References

  1. Brattström L, Wilcken DE. Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr. 2000;72(2):315–23. https://doi.org/10.1093/ajcn/72.2.315.

    Article  PubMed  Google Scholar 

  2. Sonoda M, Shoji T, Kuwamura Y, Okute Y, Naganuma T, Shima H, et al. Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus. Sci Rep. 2017;7(1):4382. https://doi.org/10.1038/s41598-017-04515-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chung KH, Chiou HY, Chen YH. Associations between serum homocysteine levels and anxiety and depression among children and adolescents in Taiwan. Sci Rep. 2017;7(1):8330. https://doi.org/10.1038/s41598-017-08568-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Troen AM. The central nervous system in animal models of hyperhomocysteinemia. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(7):1140–51. https://doi.org/10.1016/j.pnpbp.2005.06.025.

    Article  CAS  PubMed  Google Scholar 

  5. Yasar A, Gunduz K, Onur E, Calkan M. Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo. Dis Markers. 2012;33(2):85–9. https://doi.org/10.3233/DMA-2012-0908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fratoni V, Brandi ML. B vitamins, homocysteine and bone health. Nutrients. 2015;7(4):2176–92. https://doi.org/10.3390/nu7042176.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Guilliams TG. Homocysteine - a risk factor for vascular diseases: guidelines for the clinical practice. J Am Neutraceutical Assoc. 2004;7(1):11–24.

    Google Scholar 

  8. Joshi MB, Baipadithaya G, Balakrishnan A, Hegde M, Vohra M, Ahamed R, et al. Elevated homocysteine levels in type 2 diabetes induce constitutive neutrophil extracellular traps. Sci Rep. 2016;6:36362. https://doi.org/10.1038/srep36362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. https://doi.org/10.1186/1475-2891-14-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jacobsen DW. Homocysteine and vitamins in cardiovascular disease. Clin Chem. 1998;44(8):1833–43.

    CAS  PubMed  Google Scholar 

  11. Eikelboom JW, Lonn E, Genest J Jr, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med. 1999;131(5):363–75.

    Article  CAS  PubMed  Google Scholar 

  12. Ubbink JB. Assay methods for the measurement of total homocyst(e)ine in plasma. Semin Thromb Hemost. 2000;26(3):233–41. https://doi.org/10.1055/s-2000-8468.

    Article  CAS  PubMed  Google Scholar 

  13. Yin CX, Xiong KM, Huo FJ, Salamanca JC, Strongin RM. Fluorescent probes with multiple binding sites for the discrimination of Cys, Hcy, and GSH. Angew Chem Int Ed Engl. 2017;56(43):13188–98. https://doi.org/10.1002/anie.20170408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30(1-2):1–12. https://doi.org/10.1016/j.mam.2008.08.006.

    Article  CAS  PubMed  Google Scholar 

  15. Liu Y, Yu D, Ding S, Xiao Q, Guo J, Feng G. Rapid and ratiometric fluorescent detection of cysteine with high selectivity and sensitivity by a simple and readily available probe. ACS Appl Mater Interfaces. 2014;6(20):17543–50. https://doi.org/10.1021/am505501d.

    Article  CAS  PubMed  Google Scholar 

  16. Wu Q, Zhou J, Wu Y, Yu C, Hao E, Jiao L. Highly selective colorimetric and fluorescent BODIPY dyes for sensing of cysteine and/or homocysteine. New J Chem. 2016;40(2):1387–95. https://doi.org/10.1039/c5nj02346g.

    Article  CAS  Google Scholar 

  17. Yue Y, Huo F, Li X, Wen Y, Yi T, Salamanca J, et al. pH-dependent fluorescent probe that can be tuned for cysteine or homocysteine. Org Lett. 2017;19(1):82–5. https://doi.org/10.1021/acs.orglett.6b03357.

    Article  CAS  PubMed  Google Scholar 

  18. Apyari VV, Arkhipova VV, Isachenko AI, Volkov PA, Dmitrienko SG. Torocheshnikova II. Label-free gold nanoparticle-based sensing of cysteine: new peculiarities and prospects. Sens Actuators B. 2018;260:953–61. https://doi.org/10.1016/j.snb.2018.01.118.

    Article  CAS  Google Scholar 

  19. Sun J, Yang F, Zhao D, Chen C, Yang X. Integrated logic gate for fluorescence turn-on detection of histidine and cysteine based on Ag/Au bimetallic nanoclusters–Cu2+ ensemble. ACS Appl Mater Interfaces. 2015;7(12):6860–6. https://doi.org/10.1021/acsami.5b00434.

    Article  CAS  PubMed  Google Scholar 

  20. Rusin O, St. Luce NN, Agbaria RA, Escobedo JO, Jiang S, Warner IM, et al. Visual detection of cysteine and homocysteine. J Am Chem Soc. 2004;126(2):438–9. https://doi.org/10.1021/ja036297t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 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. https://doi.org/10.1021/jacs.6b12845.

    Article  CAS  PubMed  Google Scholar 

  22. Liu T, Huo F, Li J, Chao J, Zhang Y, Yin C. An off-on fluorescent probe for specifically detecting cysteine and its application in bioimaging. Sens Actuators B. 2016;237:127–32. https://doi.org/10.1016/j.snb.2016.06.080.

    Article  CAS  Google Scholar 

  23. Yue Y, Yin C, Huo F, Chao J, Zhang Y. Thiol-chromene click chemistry: a turn-on fluorescent probe for specific detection of cysteine and its application in bioimaging. Sens Actuators B. 2016;223:496–500. https://doi.org/10.1016/j.snb.2015.09.127.

    Article  CAS  Google Scholar 

  24. Liu T, Huo F, Yin C, Li J, Niu L. A highly selective fluorescence sensor for cysteine/homocysteine and its application in bioimaging. RSC Adv. 2015;5(36):28713–6. https://doi.org/10.1039/c5ra03011k.

    Article  CAS  Google Scholar 

  25. Li J, Yin C, Zhang Y, Chao J, Huo F. A long wavelength fluorescent probe for biothiols and its application in cell imaging. Anal Methods. 2016;8(37):6748–53. https://doi.org/10.1039/c6ay02150f.

    Article  CAS  Google Scholar 

  26. Su Y, Qi L, Mu X, Wang M. A fluorescent probe for sensing ferric ions in bean sprouts based on l-histidine-stabilized gold nanoclusters. Anal Methods. 2015;7(2):684–9. https://doi.org/10.1039/c4ay02186j.

    Article  CAS  Google Scholar 

  27. Xie J, Zheng Y, Ying JY. Protein-directed synthesis of highly fluorescent gold nanoclusters. J Am Chem Soc. 2009;131(3):888–9. https://doi.org/10.1021/ja806804u.

    Article  CAS  PubMed  Google Scholar 

  28. Liu H, Li M, Xia Y, Ren X. A turn-on fluorescent sensor for selective and sensitive detection of alkaline phosphatase activity with gold nanoclusters based on inner filter effect. ACS Appl Mater Interfaces. 2017;9(1):120–6. https://doi.org/10.1021/acsami.6b11920.

    Article  CAS  PubMed  Google Scholar 

  29. Chang H-C, Ho J-aA. Gold nanocluster-assisted fluorescent detection for hydrogen peroxide and cholesterol based on the inner filter effect of gold nanoparticles. Anal Chem. 2015;87(20):10362–7. https://doi.org/10.1021/acs.analchem.5b02452.

    Article  CAS  PubMed  Google Scholar 

  30. Wu Y-T, Shanmugam C, Tseng W-B, Hiseh M-M, Tseng W-L. A gold nanocluster-based fluorescent probe for simultaneous pH and temperature sensing and its application to cellular imaging and logic gates. Nanoscale. 2016;8(21):11210–6. https://doi.org/10.1039/c6nr02341j.

    Article  CAS  PubMed  Google Scholar 

  31. Nebu J, Anjali Devi JS, Aparna RS, Abha K, Sony G. Erlotinib conjugated gold nanocluster enveloped magnetic iron oxide nanoparticles–a targeted probe for imaging pancreatic cancer cells. Sens Actuators B. 2018;257:1035–43. https://doi.org/10.1016/j.snb.2017.11.017.

    Article  CAS  Google Scholar 

  32. Li R, Xu P, Tu Y, Yan J. Albumin-stabilized gold nanoclusters as viable fluorescent probes in non-titrimetric iodometry for the detection of oxidizing analytes. Microchim Acta. 2016;183(1):497–502. https://doi.org/10.1007/s00604-015-1661-y.

    Article  CAS  Google Scholar 

  33. Zhou M, Zeng C, Chen Y, Zhao S, Sfeir MY, Zhu M, et al. Evolution from the plasmon to exciton state in ligand-protected atomically precise gold nanoparticles. Nat Commun. 2016;7:13240. https://doi.org/10.1038/ncomms13240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wu Z, Jin R. On the ligand’s role in the fluorescence of gold nanoclusters. Nano Lett. 2010;10(7):2568–73. https://doi.org/10.1021/nl101225f.

    Article  CAS  PubMed  Google Scholar 

  35. Lystvet SM, Volden S, Singh G, Yasuda M, Halskau O, Glomm WR. Tunable photophysical properties, conformation and function of nanosized protein-gold constructs. RSC Adv. 2013;3(2):482–95. https://doi.org/10.1039/c2ra22479h.

    Article  CAS  Google Scholar 

  36. Wang H, Xu C, Zheng C, Xu W, Dong T, Liu K, et al. Facile synthesis and characterization of Au nanoclusters-silica fluorescent composite nanospheres. J Nanomater. 2013;2013:5. https://doi.org/10.1155/2013/972834.

    Article  CAS  Google Scholar 

  37. Meng H, Yang D, Tu Y, Yan J. Turn-on fluorescence detection of ascorbic acid with gold nanolcusters. Talanta. 2017;165(Suppl C):346–50. https://doi.org/10.1016/j.talanta.2016.12.047.

    Article  CAS  PubMed  Google Scholar 

  38. Jung HS, Han JH, Pradhan T, Kim S, Lee SW, Sessler JL, et al. A cysteine-selective fluorescent probe for the cellular detection of cysteine. Biomaterials. 2012;33(3):945–53. https://doi.org/10.1016/j.biomaterials.2011.10.040.

    Article  CAS  PubMed  Google Scholar 

  39. 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(2):2591–9. https://doi.org/10.1021/acsnano.5b07596.

    Article  CAS  PubMed  Google Scholar 

  40. Wei YJ, Liu CG, Mo LP. Ultraviolet absorption spectra of iodine, iodide ion and triiodide ion. Spectrosc Spectr Anal. 2005;25(1):86–8.

    CAS  Google Scholar 

  41. Li R, Xu P, Fan J, Di J, Tu Y, Yan J. Sensitive iodate sensor based on fluorescence quenching of gold nanocluster. Anal Chim Acta. 2014;827(Suppl C):80–5. https://doi.org/10.1016/j.aca.2014.04.013.

    Article  CAS  PubMed  Google Scholar 

  42. Chen YM, Cheng TL, Tseng WL. Fluorescence turn-on detection of iodide, iodate and total iodine using fluorescein-5-isothiocyanate-modified gold nanoparticles. Analyst. 2009;134(10):2106–12. https://doi.org/10.1039/b905426j.

    Article  CAS  PubMed  Google Scholar 

  43. Huang J, Dai W-L, Fan K. Remarkable support crystal phase effect in Au/FeOx catalyzed oxidation of 1,4-butanediol to γ-butyrolactone. J Catal. 2009;266(2):228–35. https://doi.org/10.1016/j.jcat.2009.06.011.

    Article  CAS  Google Scholar 

  44. Klyushin AY, Rocha TCR, Havecker M, Knop-Gericke A, Schlogl R. A near ambient pressure XPS study of Au oxidation. Phys Chem Chem Phys. 2014;16(17):7881–6. https://doi.org/10.1039/c4cp00308j.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the head of the Department of Chemistry, University of Kerala, Kariavattom campus, Thiruvananthapuram, for providing the platform to conduct the research. The authors also thank the director of the SICC, University of Kerala, Kariavattom campus, Thiruvananthapuram, the director of SAIF-STIC-CUSAT, Kochi, RGCB, Thiruvananthapuram, and DST-SAIF, M.G. University, Kottayam. N.J. acknowledges support for this work by the University Grants Commission, Bangalore, India, through a teacher fellowship (F.No.FIP/12th plan/KLMG035, TF: 03) under the faculty development program during the 12th plan period.

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  1. Department of Chemistry, School of Physical and Mathematical Sciences, University of Kerala, Kariavattom, Trivandrum, Kerala, 695581, India

    John Nebu, J. S. Anjali Devi, R. S. Aparna, B. Aswathy, G. M. Lekha & George Sony

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Correspondence to George Sony.

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All biological experiments were performed with the approval of the Human Ethics Committee, University of Kerala, Kerala. Informed consent was obtained from all individual participants included in the study

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Nebu, J., Anjali Devi, J.S., Aparna, R.S. et al. Potassium triiodide-quenched gold nanocluster as a fluorescent turn-on probe for sensing cysteine/homocysteine in human serum. Anal Bioanal Chem 411, 997–1007 (2019). https://doi.org/10.1007/s00216-018-1511-y

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