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Analytical and Bioanalytical Chemistry

, Volume 411, Issue 28, pp 7431–7440 | Cite as

Ratiometric detection of alkaline phosphatase based on aggregation-induced emission enhancement

  • Fei QuEmail author
  • Lingxin Meng
  • Yuqiu Zi
  • Jinmao You
Research Paper

Abstract

Alkaline phosphatase (ALP) is an important enzyme that is associated with many human diseases, so the quantitative detection of ALP is vital from a clinical perspective. Nevertheless, most fluorescent assays for monitoring ALP depend on aggregation-induced quenching (ACQ), single-signal modulation, or a “signal off” mode, which suffer from poor sensitivity, a “false positive” problem, and low signal output. In this work, we utilized the electrostatically driven self-assembly of glutathione-capped gold nanoclusters (GSH-AuNCs, which show aggregation-induced emission, AIE) and amino-modified silicon nanoparticles (SiNPs) to create a hybrid probe (SiNPs@GSH-AuNCs). This nanohybrid probe showed emission from the SiNPs at around 470 nm as well as aggregation-induced emission enhancement (AIEE) of the GSH-AuNCs at 580 nm. The AIEE of the GSH-AuNCs was quenched in the presence of KMnO4, but the AIEE was recovered by adding ascorbic acid as an oxidation–reduction reaction occurred between KMnO4 and the ascorbic acid. The fluorescence of the SiNPs remained constant whether the AIEE was quenched or not, meaning that the fluorescence of the SiNPs could be used as an internal reference. In a typical enzymatic reaction, ascorbic acid 2-phosphate is hydrolyzed by ALP to produce ascorbic acid. Therefore, the hybrid probe was shown to allow the ratiometric detection of ALP, with a linear range of 0.5–10 U L−1 and a limit of detection (LOD) of 0.23 U L−1. Finally, the proposed analytical strategy was successfully applied to detect ALP in human serum samples and to determine the concentration of an ALP inhibitor.

Graphical Abstract

Keywords

Alkaline phosphatase Aggregation-induced emission enhancement Oxidation-reduction reaction Gold nanoclusters Silicon nanoparticles 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Youth Fund Project) (21405093), the Natural Science Foundation of Shandong Province, China (ZR2019QB010), and the Scientific Research Foundation of Qufu Normal University (BSQD20130117).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical committee approval

The human serum sample experiments were performed in accordance with the guidelines from the Ethical Committee, Qufu Normal University. All serum samples were obtained from healthy volunteers with their informed consent. All studies were approved by the Ethical Committee of Qufu Normal University.

Supplementary material

216_2019_2098_MOESM1_ESM.pdf (2.5 mb)
ESM 1 (PDF 2538 kb)

References

  1. 1.
    Zheng Z, Chen PY, Xie ML, Wu CF, Luo YF, Wang WT, et al. Cell environment-differentiated self-assembly of nanofibers. J Am Chem Soc. 2016;138(35):11128–31.PubMedGoogle Scholar
  2. 2.
    Dong L, Qian JC, Hai ZJ, Xu JY, Du W, Zhong K, et al. Alkaline phosphatase-instructed self-assembly of gadolinium nanofibers for enhanced T2-weighted magnetic resonance imaging of tumor. Anal Chem. 2017;89(13):6922–5.PubMedGoogle Scholar
  3. 3.
    Deng JJ, Yu P, Wang YX, Mao LQ. Real-time ratiometric fluorescent assay for alkaline phosphatase activity with stimulus responsive infinite coordination polymer nanoparticles. Anal Chem. 2015;87(5):3080–6.PubMedGoogle Scholar
  4. 4.
    Dong L, Miao QQ, Hai ZJ, Yuan Y, Liang GL. Enzymatic hydrogelation-induced fluorescence turn-off for sensing alkaline phosphatase in vitro and in living cells. Anal Chem. 2015;87(13):6475–8.PubMedGoogle Scholar
  5. 5.
    Zheng FY, Guo SH, Zeng F, Li J, Wu SZ. Ratiometric fluorescent probe for alkaline phosphatase based on betaine-modified polyethylenimine via excimer/monomer conversion. Anal Chem. 2014;86(19):9873–9.PubMedGoogle Scholar
  6. 6.
    Yang JJ, Zheng L, Wang Y, Li W, Zhang JL, Gu JJ, et al. Guanine-rich DNA-based peroxidase mimetics for colorimetric assays of alkaline phosphatase. Biosens Bioelectron. 2016;77:549–56.PubMedGoogle Scholar
  7. 7.
    Shen CC, Li XZ, Rasooly A, Guo LY, Zhang KN, Yang MH. A single electrochemical biosensor for detecting the activity and inhibition of both protein kinase and alkaline phosphatase based on phosphate ions induced deposition of redox precipitates. Biosens Bioelectron. 2016;85:220–5.PubMedGoogle Scholar
  8. 8.
    Xiao T, Sun J, Zhao JH, Wang S, Liu GY, Yang XR. FRET effect between fluorescent polydopamine nanoparticles and MnO2 nanosheets and its application for sensitive sensing of alkaline phosphatase. ACS Appl Mater Interfaces. 2018;10(7):6560–9.PubMedGoogle Scholar
  9. 9.
    Yang L, Gao MX, Zhan L, Gong M, Zhen SJ, Huang CZ. An enzyme-induced Au@Ag core-shell nanostructure used for ultrasensitive surface-enhanced Raman scattering immunoassay of cancer biomarker. Nanoscale. 2017;9(7):2640–5.PubMedGoogle Scholar
  10. 10.
    Lakra S, Jadhav VJ, Garg SR. Development of a chromatographic method for the determination of alkaline phosphatase activity in pasteurized milk. Food Anal Methods. 2016;9(7):2002–9.Google Scholar
  11. 11.
    Nie F, Luo K, Zheng XH, Zheng JB, Song ZH. Novel preparation and electrochemiluminescence application of luminol functional-Au nanoclusters for ALP determination. Sensors Actuators B Chem. 2015;218:152–9.Google Scholar
  12. 12.
    Qian ZS, Chai LJ, Huang YY, Tang C, Shen JJ, Chen JR, et al. A real-time fluorescent assay for the detection of alkaline phosphatase activity based on carbon quantum dots. Biosens Bioelectron. 2015;68:675–80.PubMedGoogle Scholar
  13. 13.
    Ni PJ, Xie JF, Chen CX, Jiang YY, Lu YZ, Hu X. Fluorometric determination of the activity of alkaline phosphatase and its inhibitors based on ascorbic acid-induced aggregation of carbon dots. Microchim Acta. 2019;186(3):202.Google Scholar
  14. 14.
    Li DD, Zhang YP, Fan ZY, Chen J, Yu JH. Coupling of chromophores with exactly opposite luminescence behaviours in mesostructured organosilicas for high-efficiency multicolour emission. Chem Sci. 2015;6(11):6097–101.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Luo ZT, Yuan X, Yu Y, Zhang QB, Leong DT, Lee JY, et al. From aggregation-induced emission of Au(I)-thiolate complexes to ultrabright Au(0)@Au(I)-thiolate core-shell nanoclusters. J Am Chem Soc. 2012;134(40):16662–70.PubMedGoogle Scholar
  16. 16.
    Hong YN, Lam JWY, Tang BZ. Aggregation-induced emission: phenomenon, mechanism and applications. Chem Commun. 2009;4333:4332–53.Google Scholar
  17. 17.
    Hong YN, Lam JWY, Tang BZ. Aggregation-induced emission. Chem Soc Rev. 2011;40(11):5361–88.PubMedGoogle Scholar
  18. 18.
    Zhou ZX, Du Y, Dong SJ. DNA-ag nanoclusters as fluorescence probe for turn-on aptamer sensor of small molecules. Biosens Bioelectron. 2011;28:33–7.PubMedGoogle Scholar
  19. 19.
    Niu WJ, Shan D, Zhu RH, Deng SY, Cosnier S, Zhang XJ. Dumbbell-shaped carbon quantum dots/AuNCs nanohybrid as an efficient ratiometric fluorescent probe for sensing cadmium(II) ions and L-ascorbic acid. Carbon. 2016;96:1034–42.Google Scholar
  20. 20.
    Fan DQ, Shang CS, Gu WL, Wang EK, Dong SJ. Introducing ratiometric fluorescence to MnO2 nanosheet-based biosensing: a simple, label-free ratiometric fluorescent sensor programmed by cascade logic circuit for ultrasensitive GSH detection. ACS Appl Mater Interfaces. 2017;9(31):25870–7.PubMedGoogle Scholar
  21. 21.
    Qu F, Zhao LY, Han WL, You JM. Ratiometric detection of Zn2+ and Cd2+ based on self-assembled nanoarchitectures with dual emissions involving aggregation enhanced emission (AEE) and its application. J Mater Chem B. 2018;6(30):4995–5002.Google Scholar
  22. 22.
    Qu F, Xia WL, Xia L, You JM, Han WL. A ratiometric detection of heparin with high sensitivity based on aggregation-enhanced emission of gold nanoclusters triggered by silicon nanoparticles. Talanta. 2019;193:37–43.PubMedGoogle Scholar
  23. 23.
    Xue FF, Qu F, Han WL, Xia L, You JM. Aggregation-induced emission enhancement of gold nanoclusters triggered by silicon nanoparticles for ratiometric detection of protamine and trypsin. Anal Chim Acta. 2019;1046:170–8.PubMedGoogle Scholar
  24. 24.
    Ma SD, Chen YL, Feng J, Liu JJ, Zuo XW, Chen XG. One-step synthesis of water-dispersible and biocompatible silicon nanoparticles for selective heparin sensing and cell imaging. Anal Chem. 2016;88(21):10474–81.PubMedGoogle Scholar
  25. 25.
    Hu XL, Wu XM, Fang X, Li ZJ, Wang GL. Switchable fluorescence of gold nanoclusters for probing the activity of alkaline phosphatase and its application in immunoassay. Biosens Bioelectron. 2016;77:666–72.PubMedGoogle Scholar
  26. 26.
    Zhong Y, Xue F, Wei P, et al. Water-soluble MoS2 quantum dots for facile and sensitive fluorescence sensing of alkaline phosphatase activity in serum and live cells based on the inner filter effect. Nanoscale. 2018;10(45):21298–306.PubMedGoogle Scholar
  27. 27.
    Xu L, He X, Huang Y, et al. A novel near-infrared fluorescent probe for detecting intracellular alkaline phosphatase and imaging of living cells. J Mater Chem B. 2019;7(8):1284–91.Google Scholar
  28. 28.
    Tang C, Qian Z, Huang Y, et al. A fluorometric assay for alkaline phosphatase activity based on β-cyclodextrin-modified carbon quantum dots through host-guest recognition. Biosens Bioelectron. 2016;83:274–80.PubMedGoogle Scholar
  29. 29.
    Şahin ÇA, Efeçınar M, Şatıroğlu N. Combination of cloud point extraction and flame atomic absorption spectrometry for preconcentration and determination of nickel and manganese ions in water and food samples. J Hazard Mater. 2010;176(1–3):672–7.Google Scholar
  30. 30.
    Liang J, Kwok RTK, Shi H, Tang BZ, Lin B. Fluorescent light-up probe with aggregation-induced emission characteristics for alkaline phosphatase sensing and activity study. ACS Appl Mater Interfaces. 2013;5(17):8784–9.PubMedGoogle Scholar
  31. 31.
    Lin M, Huang J, Zeng F, Wu SZ. A fluorescent probe with aggregation-induced emission for detecting alkaline phosphatase and cell imaging. Chem-Asian J. 2019;14(6):802–8.Google Scholar
  32. 32.
    Zhang W, Yang H, Li N, Zhao N. A sensitive fluorescent probe for alkaline phosphatase and an activity assay based on the aggregation-induced emission effect. RSC Adv. 2018;8(27):14995–5000.Google Scholar
  33. 33.
    Li CM, Zhen SJ, Wang J, Li YF, Huang CZ. A gold nanoparticles-based colorimetric assay for alkaline phosphatase detection with tunable dynamic range. Biosens Bioelectron. 2013;43:366–71.PubMedGoogle Scholar
  34. 34.
    Hu Q, He MH, Mei YQ, Feng WJ, Jing S, Kong JM, et al. Sensitive and selective colorimetric assay of alkaline phosphatase activity with Cu(II)-phenanthroline complex. Talanta. 2017;163:146–52.PubMedGoogle Scholar
  35. 35.
    You JG, Lu CY, Kumar ASK, Tseng WL. Cerium (III)-directed assembly of glutathione-capped gold nanoclusters for sensing and imaging of alkaline phosphatase-mediated hydrolysis of adenosine triphosphate. Nanoscale. 2018;10(37):17691–8.PubMedGoogle Scholar
  36. 36.
    Zhang YY, Li YX, Zhang CY, Zhang QF, Huang XN, Yang MD, et al. Fluorescence turn-on detection of alkaline phosphatase activity based on controlled release of PEI-capped Cu nanoclusters from MnO2 nanosheets. Anal Bioanal Chem. 2017;409(20):4771–8.PubMedGoogle Scholar
  37. 37.
    Qian ZS, Chai LJ, Tang C, Huang YY, Feng H. Carbon quantum dots-based recyclable real-time fluorescence assay for alkaline phosphatase with adenosine triphosphate as substrate. Anal Chem. 2015;87(5):2966–73.PubMedGoogle Scholar
  38. 38.
    Ma XH, Du CC, Shang MX, Song WB. VS2 quantum dot label-free fluorescent probe for sensitive and selective detection of ALP. Anal Bioanal Chem. 2018;410(5):1417–26.PubMedGoogle Scholar
  39. 39.
    Yuan J, Cen Y, Kong XJ, Wu S, Liu CLW, Yu RQ, et al. MnO2-nanosheet-modified upconversion nanosystem for sensitive turn-on fluorescence detection of H2O2 and glucose in blood. ACS Appl Mater Interfaces. 2015;7(19):10548–55.PubMedGoogle Scholar
  40. 40.
    Gibbons IR, Cosson MP, Evans JA, et al. Potent inhibition of dynein adenosinetriphosphatase and of the motility of cilia and sperm flagella by vanadate. Proc Natl Acad Sci U S A. 1978;75(5):2220–4.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Huang H, Wang B, Chen M, et al. Fluorescence turn-on sensing of ascorbic acid and alkaline phosphatase activity based on graphene quantum dots. Sensors Actuators B Chem. 2016;235:356–61.Google Scholar
  42. 42.
    Al-Daghri NM, Mohammed AK, Bukhari I, et al. Efficacy of vitamin D supplementation according to vitamin D-binding protein polymorphisms. Nutrition. 2019;63:148–54.PubMedGoogle Scholar
  43. 43.
    Song P, Liu Q, Zhang Y, et al. The chemical redox modulated switch-on fluorescence of carbon dots for probing alkaline phosphatase and its application in an immunoassay. RSC Adv. 2018;8(1):162–9.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Fei Qu
    • 1
    • 2
    Email author
  • Lingxin Meng
    • 1
    • 2
  • Yuqiu Zi
    • 1
    • 2
  • Jinmao You
    • 1
    • 2
    • 3
  1. 1.The Key Laboratory of Life-Organic AnalysisQufu Normal UniversityQufuChina
  2. 2.The Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural MedicineQufu Normal UniversityQufuChina
  3. 3.Key Laboratory of Tibetan Medicine Research & Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau BiologyChinese Academy of ScienceXiningChina

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