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Bifunctional antibody and copper-based metal-organic framework nanocomposites for colorimetric α-fetoprotein sensing

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Abstract

Cu2+ are found to greatly reduce the photoinduced oxidase activity of fluorescein and then inhibit the chromogenic reaction catalyzed by fluorescein. A simple colorimetric assay for Cu2+ is established. Based on this, bifunctional nanocomposites of α-fetoprotein (AFP) antibody (Ab) and copper-based metal-organic framework (Ab2@Cu-MOF) are synthesized by the simple self-assembly of AFP Ab2, Cu2+, and 4,4′-dipyridyl: the binding site of AFP Ab2 exposed on the surface of the nanocomposites can specifically recognize AFP antigen; Cu2+ in nanocomposites can inhibit the visible light-induced activity of fluorescein. The structure of Ab2@Cu-MOF disintegrate and Cu2+ is released in an acetate buffer solution. The higher the amount of AFP antigens, the more significant the inhibitory effect. Thus, the Ab2@Cu-MOF immunoassay for AFP determination is established using 3,3′,5,5′-tetramethylbenzidine as chromogenic substrate with a detection limit of 35 pg.mL−1. This simple, cheap, and sensitive method sheds substantial light on practical clinical diagnosis. Meanwhile, the mechanism of inhibition is revealed to facilitate the targeted selection of enzyme regulators.

Diagrammatic illustration of Cu2+ detection (part a) and Ab2@Cu-MOF immunoassay for sensing α-fetoprotein based on the synthesized Ab2@Cu-MOF nanocomposites (parts a and b).

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References

  1. Luo P, Yin P, Hua R, Tan Y, Li Z, Qiu G, Chen W (2017) A large-scale, multi-center serum metabolite biomarkers identification study for the early detection of hepatocellular carcinoma. Hepatology 67:662–675

    Google Scholar 

  2. Pham NM, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Tsugane S (2013) Meat consumption and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 43:935–941

    Google Scholar 

  3. Wu Y, Guo W, Peng W, Zhao Q (2017) Enhanced fluorescence ELISA based on HAT triggering fluorescence “turn-on” with enzyme-antibody dual labeled AuNP probes for ultrasensitive detection of AFP and HBsAg. ACS Appl Mater Interfaces 9:9369–9377

    CAS  Google Scholar 

  4. Wei H, Wang E (2013) Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chem Soc Rev 42:6060–6093

    CAS  Google Scholar 

  5. Zhang L, Fan C, Liu M, Liu F, Bian S, Du S (2018) Biominerized Gold-Hemin@MOF composites with peroxidase-like and gold catalysis activities: a high-throughput colorimetric immunoassay for alpha-fetoprotein in blood by ELISA and Gold-catalytic silver staining. Sensors Actuators B Chem 266:543–552

    Article  CAS  Google Scholar 

  6. Chan CW (1998) Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281:2016–2018

    CAS  Google Scholar 

  7. Wang S, Deng W, Yang L, Tan Y, Xie Q, Yao S (2017) Copper-based metal-organic framework nanoparticles with peroxidase-like activity for sensitive colorimetric detection of Staphylococcus aureus. ACS Appl Mater Interfaces 9:24440–24445

    CAS  Google Scholar 

  8. Liao FS, Lo WS, Hsu YS, Wu CC, Wang SC, Shieh FK, Tsung CK (2017) Shielding against unfolding by embedding enzymes in metal-organic frameworks via a de novo approach. J Am Chem Soc 139:6530–6533

    CAS  Google Scholar 

  9. Hearfield DAH, Kilby BA (1958) Enzymes of the Tricarboxylic acid cycle and cytochrome oxidase in the fat body of the desert locust. Nature 181:546–547

    CAS  Google Scholar 

  10. Liu Y, Purich DL, Wu C, Wu Y, Chen T, Cui C, Wang Y (2015) Ionic functionalization of hydrophobic colloidal nanoparticles to form ionic nanoparticles with Enzymelike properties. J Am Chem Soc 137:14952–14958

    CAS  Google Scholar 

  11. Liu L, Sun CQ, Yang J, Shi Y, Long YJ, Zheng HZ (2018) Fluorescein as a visible-light-induced oxidase mimic for signal-amplified colorimetric assay of carboxylesterase by enzymatic cascade reaction. Chem Eur J 24:6148–6154

    CAS  Google Scholar 

  12. Hu Y, Cheng H, Zhao X, Wu J, Muhammad F, Lin S, Deng Y (2017) Surface-enhanced Raman scattering-active gold nanoparticles with enzyme mimicking activities for measuring glucose and lactate in living tissues. ACS Nano 11:5558–5566

    CAS  Google Scholar 

  13. Guascito MR, Malitesta C, Mazzotta E, Turco A (2008) Inhibitive determination of metal ions by an amperometric glucose oxidase biosensor : study of the effect of hydrogen peroxide decomposition. Sensors Actuators B Chem 131:394–402

    CAS  Google Scholar 

  14. Fujita T, Sakuma S, Fujimoto K, Yoshioka K, Ashida E, Nishida H, Fujimoto Y (1995) Effects of fatty acids and fatty acyl CoA esters on Cu2+ −induced conversion of xanthine dehydrogenase to oxidase in rabbit liver. Free Radic Biol Med 19:487–491

    CAS  Google Scholar 

  15. Brewer GJ (2009) The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease. J Am Coll Nutr 28:238–242

    Google Scholar 

  16. Wang C, Gao J, Tan H (2018) Integrated antibody with catalytic metal-organic framework for colorimetric immunoassay. ACS Appl Mater Interfaces 10:25113–25120

    CAS  Google Scholar 

  17. Buss H, Chan TP, Sluis KB, Domigan NM, Winterbourn CC (1997) Protein carbonyl measurement by a sensitive ELISA method. Free Radic Biol Med 23:361–366

    CAS  Google Scholar 

  18. Zhang S, Yu T, Sun MT (2014) Highly sensitive and selective fluorescence detection of copper(II) ion based on multi-ligand metal chelation. Talanta 126:185–190

    CAS  Google Scholar 

  19. Yang W, Shi X, Shi Y, Yao D, Chen S, Zhou X, Zhang B (2018) Beyond the roles in biomimetic chemistry: an insight into the intrinsic catalytic activity of an enzyme for tumor-selective phototheranostics. ACS Nano 12:12169–12180

    CAS  Google Scholar 

  20. Tian ZM, Li J, Zhang ZY (2015) Highly sensitive and robust peroxidase-like activity of porous nanorods of ceria and their application for breast cancer detection. Biomaterials 59:116–124

    CAS  Google Scholar 

  21. Huang H, Liu L, Zhang L, Zhao Q, Zhou Y, Yuan S, Tang Z (2017) Peroxidase-like activity of ethylene diamine tetraacetic acid and its application for ultrasensitive detection of tumor biomarkers and circular tumor cells. Ethylenediaminetetraacetic Acid 89:666–672

    CAS  Google Scholar 

  22. Lin LP, Song XH, Chen YY, Rong MC, Zhao TT, Wang YR, Jiang YQ, Chen X (2015) Intrinsic peroxidase-like catalytic activity of nitrogen-doped graphene quantum dots and their application in the colorimetric detection of H2O2 and glucose. Anal Chim Acta 869:89–95

    CAS  Google Scholar 

  23. An Q, Sun C, Li D, Xu K, Guo J, Wang C (2013) Peroxidase-like activity of Fe3O4@carbon nanoparticles enhances ascorbic acid-induced oxidative stress and selective damage to PC-3 prostate cancer cells. ACS Appl Mater Interfaces 5:13248–13257

    CAS  Google Scholar 

  24. Fang ZY, Huang J, Lie PC (2010) Lateral flow nucleic acid biosensor for Cu2+ detection in aqueous solution with high sensitivity and selectivity. Chem Commun 46:9043–9045

    CAS  Google Scholar 

  25. Yin HH, Kuang H, Liu LQ (2014) A ligation DNAzyme-induced magnetic nanoparticles assembly for ultrasensitive detection of copper ions. ACS Appl Mater Interfaces 6:4752–4757

    CAS  Google Scholar 

  26. Yin K, Wu YX (2016) A sensitive fluorescent biosensor for the detection of copper ion inspired by biological recognition element pyoverdine. Sensors Actuators B Chem 232:257–263

    CAS  Google Scholar 

  27. Zhang N, Qu F (2013) Sensitive signal-on fluorescent sensing for copper ions based on the polyethyleneimine-capped silver nanoclusters-cysteine system. Anal Chim Acta 791:46–50

    CAS  Google Scholar 

  28. Dong YQ, Wang RX (2012) Polyamine-functionalized carbon quantum dots as fluorescent probes for selective and sensitive detection of copper ions. Anal Chem 84:6220–6224

    CAS  Google Scholar 

  29. Xu XY (2010) Colorimetric Cu2+ detection using DNA-modified gold-nanoparticle aggregates as probes and click chemistry. Small 6:623–626

    CAS  Google Scholar 

  30. Schwarze T, Kelling A, Mueller H (2012) N-2-pyridinylmethyl-N'-arylmethyl-diaminomaleonitriles: new highly selective chromogenic chemodosimeters for copper(II). Chem Eur J 18:10506–10510

    CAS  Google Scholar 

  31. Cui Y, Wang XW, Zhang Q (2019) Colorimetric copper ion sensing in solution phase and on paper substrate based on catalytic decomposition of S-nitrosothiol. Anal Chim Acta 1053:155–161

    CAS  Google Scholar 

  32. Guo NH, You X, Wu YT (2020) Continuous fluorometric method for determining the monophenolase activity of tyrosinase on L-tyrosine, through quenching L-DOPA fluorescence by borate. Anal Chem 92:5780–5786

    CAS  Google Scholar 

  33. Griffith OH, Waggoner AS (1969) Nitroxide free radicals: spin labels for probing biomolecular structure. Acc Chem Res 2:17–24

    CAS  Google Scholar 

  34. Jiao L, Wang Y, Jiang HL, Xu Q (2017) Metal-organic frameworks as platforms for catalytic applications. Adv Mater 30:1703663

    Google Scholar 

  35. Han Y, Zhang F, Gong H, Cai C (2018) Double G-quadruplexes in a copper nanoparticle based fluorescent probe for determination of HIV genes. Microchim Acta 186:30

    Google Scholar 

  36. Ye T, Peng Y, Yuan M (2019) Target-induced in-situ formation of fluorescent DNA-templated copper nanoparticles by a catalytic hairpin assembly: application to the determination of DNA and thrombin. Microchim Acta 186:760

    CAS  Google Scholar 

  37. Tang D, Yuan R, Chai Y (2006) Electrochemical immuno-bioanalysis for carcinoma antigen 125 based on thionine and gold nanoparticles-modified carbon paste interface. Anal Chim Acta 564:158–165

    CAS  Google Scholar 

  38. Lin Y (2019) Enzyme-free multicolor biosensor based on Cu2+-modified carbon nitride nanosheets and gold nanobipyramids for sensitive detection of neuron specific enolase. Sensors Actuators B Chem 283:138–145

    CAS  Google Scholar 

  39. Xiang HP, Wang YL (2018) A redox cycling-amplified electrochemical immunosensor for α-fetoprotein sensitive detection via polydopamine nanolabels. Nanoscale 10:13572–13580

    CAS  Google Scholar 

  40. Bi S, Yan YM, Yang XY (2010) Gold nanolabels for new enhanced chemiluminescence immunoassay of alpha-fetoprotein based on magnetic beads. Chem Eur J 15:4704–4709

    Google Scholar 

  41. Chen CX, Zhao JH (2018) Fluorescence immunoassay based on the phosphate-triggered fluorescence turn-on detection of alkaline phosphatase. Anal Chem 90:3505–3511

    CAS  Google Scholar 

  42. Ren RR, Cai GN (2018) Metal-polydopamine framework: an innovative signal-generation tag for colorimetric immunoassay. Anal Chem 90:11099–11105

    CAS  Google Scholar 

  43. Zhang XB, Li YY, Lv H (2018) Sandwich-type electrochemical immunosensor based on au@Ag supported on functionalized phenolic resin microporous carbon spheres for ultrasensitive analysis of α-fetoprotein. Biosens Bioelectron 106:142–148

    CAS  Google Scholar 

  44. Liu YC, Chen JY (2017) The preparation of dual-functional hybrid nanoflower and its application in the ultrasensitive detection of disease-related biomarker. Biosens Bioelectron 92:68–73

    CAS  Google Scholar 

  45. Hu XM (2019) Colorimetric sensing of alkaline phosphatase and alpha-fetoprotein based on the photoinduced oxidase activity of fluorescein. New J Chem 43:4525–4530

    CAS  Google Scholar 

  46. Wang HM, Chen YQ, Wang H, Liu XQ, Zhou X, Wang F (2019) DNAzyme-loaded metal-organic frameworks (MOFs) for self-sufficient gene therapy. Angew Chem 58:7380–7384

    CAS  Google Scholar 

  47. Lin Z, Li MJ, Lv S, Zhang K, Lu M, Tang D (2017) In situ synthesis of fluorescent polydopamine nanoparticles coupled with enzyme-controlled dissolution of MnO2 nanoflakes for a sensitive immunoassay of cancer biomarkers. J Mater Chem B 5:8506–8513

    CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 21405124, 21175110).

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Authors and Affiliations

  1. Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Beibei, Chongqing, 400715, China

    Xuemei Hu, Zixuan Wei, Chaoqun Sun, Yijuan Long & Huzhi Zheng

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  1. Xuemei Hu
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  2. Zixuan Wei
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  3. Chaoqun Sun
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Correspondence to Huzhi Zheng.

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Hu, X., Wei, Z., Sun, C. et al. Bifunctional antibody and copper-based metal-organic framework nanocomposites for colorimetric α-fetoprotein sensing. Microchim Acta 187, 465 (2020). https://doi.org/10.1007/s00604-020-04427-z

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