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An electrochemiluminescence biosensor for p53 antibody based on Zn-MOF/GO nanocomposite and Ag+-DNA amplification

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Abstract

An ultrasensitive electrochemiluminescence biosensor was established based on the Zn-MOF/GO nanocomposite. Ag(I)-embedded DNA complexes were used as a signal amplification reagent. In this work, 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) and Zn2+ were integrated into a porphyrin paddlewheel framework (Zn-MOF) by a hydrothermal method. The synthesized Zn-MOF material has electrochemiluminescence property, and the luminescence intensity is improved after being composited with graphene oxide (GO). Based on the composite material, we constructed an ultrasensitive ECL biosensor for the p53 antibody detection. The composite material acted as an admirable substrate and then loaded plenty of p53 antigens to recognize the target (p53 antibody) accurately. Because of the bridging effect of streptavidin and biotin-conjugated goat anti-rabbit IgG (bio-ab2), the rich-C DNA with positive correlation with the target was modified on the electrode and then captured the co-reactant accelerator Ag+ to amplify the signal. Therefore, the ECL biosensor response increases with increasing p53 antibody concentration. In the range 0.1 fg/mL–0.01 ng/mL, the response signal of the biosensor has a good linear relationship with the p53 antibody concentration. The detection limit is 0.03 fg/mL (S/N = 3). Impressively, the biosensor not only featured high sensitivity, good stability, and excellent specificity for the detection of p53 antibody, but also provides a new way for early detection of cancer.

Schematic representation of the electrochemiluminescence sensor based on a Zn-MOF/GO nanocomposite, which can be applied to the determination of p53 antibody.

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References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108

    Article  Google Scholar 

  2. Yeo JC, Park JY, Bae WJ, Lee YS, Kim BH (2009) Label-free electrochemical detection of the p53 core domain protein on its antibody immobilized electrode. Anal Chem 81:4770–4777

    Article  CAS  Google Scholar 

  3. Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–310

    Article  CAS  Google Scholar 

  4. Yang LL, Tao YZ, Yue GY, Li RB, Qiu B, Guo LH, Lin ZY, Yang H (2016) Highly selective and sensitive electrochemiluminescence biosensor for p53 DNA sequence based on nicking endonuclease assisted target recycling and hyperbranched rolling circle amplification. Anal Chem 88:5097–5103

    Article  CAS  Google Scholar 

  5. Lane DP (1992) Cancer. p53, guardian of the genome. Nature 358:15–16

    Article  CAS  Google Scholar 

  6. Schlichtholz B (1992) The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot. Cancer Res 52:6380–6384

    CAS  Google Scholar 

  7. Winter SF (1992) Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res 52:4168–4174

    CAS  Google Scholar 

  8. Atta MM, El-Masry SA, Abdel-Hameed M, Baiomy HA, Ramadan NE (2008) Value of serum anti-p53 antibodies as a prognostic factor in Egyptian patients with hepatocellular carcinoma. Clin Biochem 41:1131–1139

    Article  CAS  Google Scholar 

  9. Anderson KS, Wong J, Vitonis A, Crum CP, Sluss PM, Labaer J, Cramer D (2010) P53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer. Cancer Epidemiol Biomarkers Prev 19:859–868

    Article  CAS  Google Scholar 

  10. Lubin R, Zalcman G, Bouchet L, Tredanel J, Legros Y, Cazals D, Hirsch A, Soussi T (1995) Serum p53 antibodies as early markers of lung cancer. Nat Med 1:701–702

    Article  CAS  Google Scholar 

  11. Mudenda B, Green JA, Green B, Jenkins JR, Robertson L, Tarunina M, Leinster SJ, The relationship between serum p53 autoantibodies and characteristics of human breast cancer (1994) Br J Cancer 69:1115–1119

    Article  CAS  Google Scholar 

  12. Portefaix J, Fanutti C, Granier C, Crapez E, Perham R, Grenier J, Pau B, Del Rio M (2002) Detection of anti-p53 antibodies by ELISA using p53 synthetic or phage-displayed peptides. J Immunol Methods 259:65–75

    Article  CAS  Google Scholar 

  13. Elshafey R, Siaj M, Tavares AC (2016) Au nanoparticle decorated graphene nanosheets for electrochemical immunosensing of p53 antibodies for cancer prognosis. Analyst 141:2733–2740

    Article  CAS  Google Scholar 

  14. Ge JJ, Zhao Y, Gao XS, Li HK, Jie GF (2019) Versatile electrochemiluminescence and photoelectrochemical detection of glutathione using Mn2+ substitute target by DNA walker-induced allosteric switch and signal amplification. Anal Chem 91:14117–14124

    Article  CAS  Google Scholar 

  15. Ge JJ, Zhao Y, Li CL, Jie GF (2019) Versatile electrochemiluminescence and electrochemical “on−off” assays of methyltransferases and aflatoxin B1 based on a novel multifunctional DNA nanotube. Anal Chem 91:3546–3554

    Article  CAS  Google Scholar 

  16. Wang J, Zhuo Y, Zhou Y, Wang HJ, Yuan R, Chai YQ (2016) Ceria doped zinc oxide nanoflowers enhanced luminol-based electrochemiluminescence immunosensor for amyloid-β detection. ACS Appl Mater Interfaces 8:12968–12975

    Article  CAS  Google Scholar 

  17. Ke H, Sha H, Wang Y, Guo W, Zhang X, Wang Z, Huang C, Jia N (2017) Electrochemiluminecence resonance energy transfer system between GNRs and Ru(bpy)32+: application in magnetic aptasensor for β-amyloid. Biosens Bioelectron 100:266–273

    Article  Google Scholar 

  18. Wen W, Yan X, Zhu C, Du D, Lin Y (2017) Recent advances in electrochemical immunosensors. Anal Chem 89:138–156

    Article  CAS  Google Scholar 

  19. Hu GB, Xiong CY, Liang WB, Zeng XS, Xu HL, Yang Y, Yao LY, Yuan R, Xiao DR (2018) Highly stable mesoporous luminescence-functionalized MOF with excellent electrochemiluminescence property for ultrasensitive immunosensor construction. ACS Appl Mater Interfaces 10:15913–15919

    Article  CAS  Google Scholar 

  20. Cho KG, Lee JI, Lee S, Hong KY, Kang MS, Lee KH (2020) Light-emitting devices based on electrochemiluminescence gels. Adv Funct Mater 2020:1907936

    Article  Google Scholar 

  21. Babamiri B, Bahari D, Salimi A (2020) Highly sensitive bioaffinity electrochemiluminescence sensors: recent advances and future directions. Biosens Bioelectron 142:111530

    Article  Google Scholar 

  22. Valenti G, Rampazzo E, Kesarkar S, Genovese D, Fiorani A, Zanut A, Palomba F, Marcaccio M, Paolucci F, Prodi L (2018) Electrogenerated chemiluminescence from metal complexes-based nanoparticles for highly sensitive sensors applications. Coord Chem Rev 367:65–81

    Article  CAS  Google Scholar 

  23. Hou LL, Zhou BB (2019) Electrochemiluminescent biosensors for the detection of microRNAs: a review. Int J Electrochem Sci 14:2489–2508

    Article  CAS  Google Scholar 

  24. Abednatanzi S, Derakhshandeh PG, Depauw H, Coudert FX, Vrielinck H, Voort PVD, Leus K (2019) Mixed-metal metal–organic frameworks. Chem Soc Rev 48:2497–2658

    Article  Google Scholar 

  25. Lin X, Jia JH, Zhao XB, Thomas KM, Blake AJ, Walker GS, Champness NR (2010) High H2 adsorption by coordination-framework materials. Angew Chem Int Ed Eng 118:7518–7524

    Article  Google Scholar 

  26. Li JR, Kuppler RJ, Zhou HC (2009) Selective gas adsorption and separation in metal–organic frameworks. Chem Soc Rev 38:1477–1504

    Article  CAS  Google Scholar 

  27. Liu Q, Yang Y, Liu XP, Wei YP, Mao CJ, Chen JS, Niu HL, Song JM, Zhang SY, Jin BK, Jiang M (2016) A facile in situ synthesis of MIL-101-CdSe nanocomposites for ultrasensitive electrochemiluminescence detection of carcinoembryonic antigen. Sensors Actuators B Chem 242:1073–1078

    Article  Google Scholar 

  28. Murray LJ, Dinca M, Long JR (2009) Hydrogen storage in metal–organic frameworks. Chem Soc Rev 38:1294–1314

    Article  CAS  Google Scholar 

  29. Dong X, Zhao G, Liu L, Li X, Wei Q, Cao W (2018) Ultrasensitive competitive method-based electrochemiluminescence immunosensor for diethylstilbestrol detection based on Ru(bpy)32+, as luminophor encapsulated in metal–organic frameworks UiO-67. Biosens Bioelectron 110:201–206

    Article  CAS  Google Scholar 

  30. Zhao GH, Wang YG, Li XJ, Yue Q, Dong X, Du B, Cao W, Wei Q (2019) Dual-quenching electrochemiluminescence strategy based on three-dimensional metal−organic frameworks for ultrasensitive detection of amyloid-β. Anal Chem 91:1989–1996

    Article  CAS  Google Scholar 

  31. Luo D, Huang B, Wang L, Idris AM, Wang SX, Lu XQ (2015) Cathodic electrochemiluminescence of meso-tetra(4-carboxyphenyl) porphyrin/potassium peroxydisulfate system in aqueous media. Electrochim Acta 151:42–49

    Article  CAS  Google Scholar 

  32. Zhao YM, Ling J, Li SG, Li M, Liu AR, Liu SQ (2018) Synthesis of porphyrin-based two-dimensional metal–organic framework nanodisk with small size and few layers. J Mater Chem A 6:2828–2833

    Article  CAS  Google Scholar 

  33. Ge JJ, Li CL, Zhao Y, Yu XJ, Jie GF (2019) Versatile “on–off” biosensing of thrombin and miRNA based on Ag(I) ion-enhanced or Ag nanocluster-quenched electrochemiluminescence coupled with hybridization chain reaction amplification. Chem Commun 55:7350–7353

    Article  CAS  Google Scholar 

  34. Ye L, Gao Y, Cao SY, Chen H, Yao YN, Hou JG, Sun LC (2018) Assembly of highly efficient photocatalytic CO2 conversion systems with ultrathin two-dimensional metal–organic framework nanosheets. Appl Catal B Environ 227:54–60

    Article  CAS  Google Scholar 

  35. Jahan M, Bao QL, Loh KP (2012) Electrocatalytically active graphene–porphyrin MOF composite for oxygen reduction reaction. J Am Chem Soc 134:6707–6713

    Article  CAS  Google Scholar 

  36. Sadeghi N, Sharifnia S, Sheikh Arabi M (2016) A porphyrin-based metal organic framework for high rate photoreduction of CO2 to CH4 in gas phase J CO2 Util. 16: 450–457

  37. Wang X, Wang QX, Wang QH, Gao F, Yang YZ, Guo HX (2014) Highly dispersible and stable copper terephthalate metal−organic framework−graphene oxide nanocomposite for an electrochemical sensing application. ACS Appl Mater Interfaces 6:11573–11580

    Article  CAS  Google Scholar 

  38. Ang HX, Hong L (2017) Polycationic polymer-regulated assembling of 2D MOF nanosheets for high-performance nanofiltration. ACS Appl Mater Interfaces 9:28079–28088

    Article  CAS  Google Scholar 

  39. Liu M, Xie K, Nothling MD, Gurr PA, Tan SSL, Fu Q, Webley PA, Qiao GG (2018) Ultrathin metal-organic framework nanosheets as a gutter layer for flexible composite gas separation membranes. ACS Nano 12:11591–11599

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (21976001), Natural Science Foundation of Anhui Province (1808085QB53), and open fund for Discipline Construction of Institute of Physical Science and Information Technology.

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Correspondence to Jing-Shuai Chen or Chang-jie Mao.

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The protocol of this study was approved by the medical ethics committee of The First Affiliated Hospital of Anhui Medical University. Human Serum Samples were also provided by The First Affiliated Hospital of Anhui Medical University. The blood samples (2 mL) of the participants were collected after informed written consent was provided by the subjects.

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Wei, Yp., Zhang, Yw., Chen, JS. et al. An electrochemiluminescence biosensor for p53 antibody based on Zn-MOF/GO nanocomposite and Ag+-DNA amplification. Microchim Acta 187, 455 (2020). https://doi.org/10.1007/s00604-020-04425-1

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