Microchimica Acta

, 186:75 | Cite as

Gold nanoparticles conjugated to bimetallic manganese(II) and iron(II) Prussian Blue analogues for aptamer-based impedimetric determination of the human epidermal growth factor receptor-2 and living MCF-7 cells

  • Nan ZhouEmail author
  • Fangfang Su
  • Zhenzhen Li
  • Xu Yan
  • Chunlin Zhang
  • Bin Hu
  • Linghao He
  • Minghua Wang
  • Zhihong ZhangEmail author
Original Paper


An aptamer-based assay is described for the determination of trace levels of the cancer marker human epidermal growth factor receptor-2 (HER2) and living MCF-7 cells. The method is based on the use of a bimetallic MnFe Prussian blue analogue coupled to gold nanoparticles (MnFePBA@AuNP). Compared to pristine MnFe PBA nanocubes, the series of MnFePBA@AuNP exhibits a core-shell spherical nanostructure, and the shell thickness decreases from 99.9 nm down to 49.3 nm on increasing the fraction of AuNPs. The composite was placed on a gold electrode and incubated with the aptamer solution through electrostatic interaction. Then the modified electrode was employed to detect HER2 and MCF-7 cells using [Fe(CN)6]3−/4− as redox probe and displays good responses to both of them. Electrochemical impedance spectroscopy data show that the signal variation between each step during the whole procedure for the HER2 and MCF-7 cells detection can be embodied as the resistance value change between the [Fe(CN)6]3−/4− and electrode surface. The assay has a very low detection limit (0.247 pg∙mL−1) and works in the 0.001–1.0 ng∙mL−1 HER2 concentration range. It was also used to sense HER2 in MCF-7 cells, and this results in an assay that works within the 500–5 × 104 cell∙mL−1 cell concentration range and a 36 cell∙mL−1 detection limit. Furthermore, the aptamer-based assay is selective, acceptably reproducible, stable, and well feasible for the detection of HER2 and living MCF-7 cells in human serum.

Graphical abstract

Schematic of an electrochemical aptasensor based on the bimetallic MnFe Prussian blue analogue (MnFe PBA) coupling with gold nanoparticles (represented by MnFePBA@AuNPs). It was employed as the aptasensor for human epidermal growth factor receptor-2 (HER2), and living MCF-7 cells.


HER2 detection Living MCF-7 cell detection MnFe Prussian blue analogue Au nanoparticles Cyclic voltammetry Electrochemical impedance spectroscopy Sensitivity Selectivity Reproducibility Stability 



This work was supported by Programs for the National Natural Science Foundation of China (NSFC: Account Nos. U1604127, U1704256, and 21401168), and Innovative Technology Team of Henan Province (CXTD2014042).

Compliance with ethical standards

The author(s) declare that they have no competing interests.

Supplementary material

604_2018_3184_MOESM1_ESM.doc (19.7 mb)
ESM 1 (DOC 19.6 mb)


  1. 1.
    Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S, Saunders C, Roche N, Mansel RE, von Minckwitz G, Bonanni B, Palva T, Howell A (2014) Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 383:1041–1048CrossRefGoogle Scholar
  2. 2.
    Guadagnoli E, Ward P (1998) Patient participation in decision-making. Soc Sci Med 47:329–339CrossRefGoogle Scholar
  3. 3.
    Eletxigerra U, Martinez-Perdiguero J, Barderas R, Pingarrón JM, Campuzano S, Merino S (2016) Surface plasmon resonance immunosensor for ErbB2 breast cancer biomarker determination in human serum and raw cancer cell lysates. Anal Chim Acta 905:156–162CrossRefGoogle Scholar
  4. 4.
    Kricka LJ (1994) Selected strategies for improving sensitivity and reliability of immunoassays. Clin Chem 40:347–357PubMedGoogle Scholar
  5. 5.
    Li X, Yang J, Xie J, Jiang B, Yuan R, Xiang Y (2018) Cascaded signal amplification via target-triggered formation of aptazyme for sensitive electrochemical detection of ATP. Biosens Bioelectron 102:296–300CrossRefGoogle Scholar
  6. 6.
    Cho EJ, Lee J, Ellington AD (2009) Applications of aptamers as sensors. Annu Rev Anal Chem 2:241–264CrossRefGoogle Scholar
  7. 7.
    Eivazzadeh-Keihan R, Pashazadeh-Panahi P, Baradaran B, Maleki A, Hejazi M, Mokhtarzadeh A, de la Guardia M (2018) Recent advances on nanomaterial based electrochemical and optical aptasensors for detection of cancer biomarkers. Trac-Trend Anal Chem 100:103–115CrossRefGoogle Scholar
  8. 8.
    Zhang D, Zhang F, Cui Y, Deng Q, Krause S, Zhou Y, Zhang X (2012) A label-free aptasensor for the sensitive and specific detection of cocaine using supramolecular aptamer fragments/target complex by electrochemical impedance spectroscopy. Talanta 92:65–71CrossRefGoogle Scholar
  9. 9.
    Zhang H, Zhang H, Aldalbahi A, Zuo X, Fan C, Mi X (2017) Fluorescent biosensors enabled by graphene and graphene oxide. Biosens Bioelectron 89:96–106CrossRefGoogle Scholar
  10. 10.
    Song Y, Duan F, Zhang S, Tian J, Zhang Z, Wang Z, Liu C, Xu W, Du M (2017) Iron oxide@mesoporous carbon architectures derived from an Fe(II)-based metal organic framework for highly sensitive oxytetracycline determination. J Mater Chem A 5:19378–19389CrossRefGoogle Scholar
  11. 11.
    Kwon OS, Park SJ, Hong J, Han A, Lee JS, Lee JS, Oh JH, Jang J (2012) Flexible FET-type VEGF aptasensor based on nitrogen-doped graphene converted from conducting polymer. ACS Nano 6:1486–1493CrossRefGoogle Scholar
  12. 12.
    Yazdanparast S, Benvidi A, Banaei M, Nikukar H, Tezerjani MD, Azimzadeh M (2018) Dual-aptamer based electrochemical sandwich biosensor for MCF-7 human breast cancer cells using silver nanoparticle labels and a poly(glutamic acid)/MWNT nanocomposite. Microchim Acta 185:405CrossRefGoogle Scholar
  13. 13.
    Gervais C, Languille M, Moretti G, Réguer S (2015) X-ray photochemistry of prussian blue cellulosic materials: evidence for a substrate-mediated redox process. Langmuir 31:8168–8175CrossRefGoogle Scholar
  14. 14.
    Karyakin AA, Karyakina EE, Gorton L (2000) Amperometric biosensor for glutamate using prussian blue-based “artificial peroxidase” as a transducer for hydrogen peroxide. Anal Chem 72:1720–1723CrossRefGoogle Scholar
  15. 15.
    Haghighi B, Varma S, Alizadeh Sh FM, Yigzaw Y, Gorton L (2004) Prussian blue modified glassy carbon electrodes-study on operational stability and its application as a sucrose biosensor. Talanta 64:3–12CrossRefGoogle Scholar
  16. 16.
    Wang Y, Bao S, Li R, Zhao G, Wang Z, Zhao Z, Chen Q (2015) Universal strategy for homogeneously doping noble metals into cyano-bridged coordination polymers. ACS Appl Mater Inter 7:2088–2096CrossRefGoogle Scholar
  17. 17.
    Yang T, Gao Y, Liu Z, Xu J, Lu L, Yu Y (2017) Three-dimensional gold nanoparticles/prussian blue-poly(3,4-ethylenedioxythiophene) nanocomposite as novel redox matrix for label-free electrochemical immunoassay of carcinoembryonic antigen. Sensor Actuat B-Chem 239:76–84CrossRefGoogle Scholar
  18. 18.
    Pi Y, Ma L, Zhao P, Cao Y, Gao H, Wang C, Li Q, Dong S, Sun J (2018) Facile green synthetic graphene-based co-Fe Prussian blue analogues as an activator of peroxymonosulfate for the degradation of levofloxacin hydrochloride. J Colloid Interf Sci 526:18–27CrossRefGoogle Scholar
  19. 19.
    Wang M, Yang L, Hu B, Liu J, He L, Jia Q, Song Y, Zhang Z (2018) Bimetallic NiFe oxide structures derived from hollow NiFe Prussian blue nanobox for label-free electrochemical biosensing adenosine triphosphate. Biosens Bioelectron 113:16–24CrossRefGoogle Scholar
  20. 20.
    Fan Z, Shi J, Gao C, Gao G, Wang B, Niu C (2017) Rationally designed porous MnOx-FeOx nanoneedles for low-temperature selective catalytic reduction of NOx by NH3. Acs Appl Mater Inter 9:16117–16127CrossRefGoogle Scholar
  21. 21.
    Lee J, Cho H, Choi H, Lee J, Choi J (2018) Application of gold nanoparticle to plasmonic biosensors. Int J Mol Sci 19:2021CrossRefGoogle Scholar
  22. 22.
    Liu J, Irudayaraj JMK (2016) Non-fluorescent quantification of single mRNA with transient absorption microscopy. Nanoscale 8:19242–19248CrossRefGoogle Scholar
  23. 23.
    Shen C, Zeng K, Luo J, Li X, Yang M, Rasooly A (2017) Self-assembled DNA generated electric current biosensor for HER2 analysis. Anal Chem 89:10264–10269CrossRefGoogle Scholar
  24. 24.
    Xiong P, Zeng G, Zeng L, Wei M (2015) Prussian blue analogues Mn[Fe(CN)6]0.6667·nH2O cubes as an anode material for lithium-ion batteries. Dalton T 44:16746–16751CrossRefGoogle Scholar
  25. 25.
    Chiorcea-Paquim A, Oliveira-Brett MA (2016) Guanine quadruplex electrochemical aptasensors. Chemosensors 4:13CrossRefGoogle Scholar
  26. 26.
    Arya SK, Zhurauski P, Jolly P, Batistuti MR, Mulato M, Estrela P (2018) Capacitive aptasensor based on interdigitated electrode for breast cancer detection in undiluted human serum. Biosens Bioelectron 102:106–112CrossRefGoogle Scholar
  27. 27.
    Li T, Si Z, Hu L, Qi H, Yang M (2012) Prussian blue-functionalized ceria nanoparticles as label for ultrasensitive detection of tumor necrosis factor-α. Sensor Actuat B-Chem 171-172:1060–1065CrossRefGoogle Scholar
  28. 28.
    Piernas-Muñoz MJ, Castillo-Martínez E, Roddatis V, Armand M, Rojo T (2014) K1-xFe2+x/3(CN)6·yH2O, Prussian blue as a displacement anode for lithium ion batteries. J Power Sources 271:489–496CrossRefGoogle Scholar
  29. 29.
    Yu S, Kim YH, Lee SY, Song HD, Yi J (2014) Hot-electron-transfer enhancement for the efficient energy conversion of visible light. Angew Chem Int Edit 53:11203–11207CrossRefGoogle Scholar
  30. 30.
    Liu C, Sun C, Tian J, Wang Z, Ji H, Song Y, Zhang S, Zhang Z, He L, Du M (2017) Highly stable aluminum-based metal-organic frameworks as biosensing platforms for assessment of food safety. Biosens Bioelectron 91:804–810CrossRefGoogle Scholar
  31. 31.
    Ferreira AAP, Fugivara CS (2011) Yamanaka H. Benedetti AV, Preparation and characterization of imunosensors for disease diagnosisGoogle Scholar
  32. 32.
    Ma S, Hu Y, Zhang Q, Guo Z, Wang S, Shen Q, Liu C, Liu Z (2018) Adenine/au complex-dependent versatile electrochemical platform for ultrasensitive DNA-related enzyme activity assay. Sensor Actuat B-Chem 273:760–770CrossRefGoogle Scholar
  33. 33.
    Mohammad Danesh N, Ramezani M, Sarreshtehdar Emrani A, Abnous K, Taghdisi SM (2016) A novel electrochemical aptasensor based on arch-shape structure of aptamer-complimentary strand conjugate and exonuclease I for sensitive detection of streptomycin. Biosens Bioelectron 75:123–128CrossRefGoogle Scholar
  34. 34.
    Qureshi A, Gurbuz Y, Niazi JH (2015) Label-free capacitance based aptasensor platform for the detection of HER2/ErbB2 cancer biomarker in serum. Sensor Actuat B-Chem 220:1145–1151CrossRefGoogle Scholar
  35. 35.
    Harris K, Fujita D, Fujita M (2013) Giant hollow MnL2n spherical complexes: structure, functionalisation and applications. Chem Commun 49:6703–6712CrossRefGoogle Scholar
  36. 36.
    Hsu C, Lien C, Wang C, Harroun SG, Huang C, Chang H (2016) Immobilization of aptamer-modified gold nanoparticles on BiOCl nanosheets: tunable peroxidase-like activity by protein recognition. Biosens Bioelectron 75:181–187CrossRefGoogle Scholar
  37. 37.
    Hua X, Zhou Z, Yuan L, Liu S (2013) Selective collection and detection of MCF-7 breast cancer cells using aptamer-functionalized magnetic beads and quantum dots based nano-bio-probes. Anal Chim Acta 788:135–140CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Nan Zhou
    • 1
    Email author
  • Fangfang Su
    • 2
  • Zhenzhen Li
    • 2
  • Xu Yan
    • 1
  • Chunlin Zhang
    • 1
  • Bin Hu
    • 2
  • Linghao He
    • 2
  • Minghua Wang
    • 2
  • Zhihong Zhang
    • 2
    Email author
  1. 1.Department of OrthopedicsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouPeople’s Republic of China
  2. 2.Henan Provincial Key Laboratory of Surface and Interface ScienceZhengzhou University of Light IndustryZhengzhouPeople’s Republic of China

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