Skip to main content

Advertisement

Springer Nature Link
Log in

Sandwich-type supersensitive electrochemical aptasensor of glypican-3 based on PrGO-Hemin-PdNP and AuNP@PoPD

  • Original Paper
  • Published:
Microchimica Acta Aims and scope Submit manuscript

Abstract

A new sandwich-type electrochemical biosensing platform was developed by gold @polyphthalenediamine nanohybrids (AuNP@PoPD) as the sensing platform and phosphorus doped reduced graphene oxide-hemin-palladium nanoparticles (PrGO-Hemin-PdNP) as the signal amplifier for phosphatidylinositol proteoglycan 3 (GPC3). AuNP@PoPD, co-electrodeposited into the screen printed electrode with high conductivity and stability, is dedicated to assembling the primary GPC3 aptamer (GPC3Apt). The second GPC3Apt immobilized on the high conductivity and large surface area of PrGO-Hemin-PdNP was utilized as an electrochemical signal reporter by hemin oxidation (PrGO-Hemin-PdNP-GPC3Apt). In the range 0.001–10.0 ng/mL, the hemin oxidation current signal of the electrochemical aptasensor increased log-linearly with the concentration of GPC3, the lowest detection limit was 0.13 pg/mL, and the sensitivity was 2.073 μA/μM/cm2. The aptasensor exhibited good sensing performance in a human serum sample with the relative error of 4.31–8.07%. The sandwich sensor showed good selectivity and stability for detection GPC3 in human serum samples, providing a new efficient and sensitive method for detecting HCC markers.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Deng K, Xing J, Xu G, Jin B, Wan X, Zheng Y, Du S, Sang X (2023) Urinary biomarkers for hepatocellular carcinoma: current knowledge for clinicians. Cancer Cell Int 23:239. https://doi.org/10.1186/s12935-023-03092-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Malik A, Thanekar U, Amarachintha S, Mourya R, Nalluri S, Bondoc A, Shivakumar P (2021) “Complimenting the complement”: mechanistic insights and opportunities for therapeutics in hepatocellular carcinoma. Front Oncol 10:30. https://doi.org/10.3389/fonc.2020.627701

    Article  Google Scholar 

  3. Debes JD, Romagnoli PA, Prieto J, Arrese M, Mattos AZ, Boonstra A (2021) Serum biomarkers for the prediction of hepatocellular carcinoma. Cancers 13:13. https://doi.org/10.3390/cancers13071681

    Article  CAS  Google Scholar 

  4. Turshudzhyan A, Wu GY (2021) Persistently rising alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: a review. J Clin Tran Hepatol 10(1):159–163. https://doi.org/10.14218/jcth.2021.00176

    Article  Google Scholar 

  5. Piñero F, Dirchwolf M, Pessôa MG (2020) Biomarkers in hepatocellular carcinoma: diagnosis, prognosis and treatment response assessment. Cells 9:27. https://doi.org/10.3390/cells9061370

    Article  CAS  Google Scholar 

  6. Liu MY, Huang L, Wu JF, Zhang HB, Ai WB, Zhang RT (2022) Possible roles of Golgi protein-73 in liver diseases. Ann Hepatol 27:6. https://doi.org/10.1016/j.aohep.2022.100720

    Article  CAS  Google Scholar 

  7. Force M, Park G, Chalikonda D, Roth C, Cohen M, Halegoua-DeMarzio D, Hann HW (2022) Alpha-fetoprotein (AFP) and AFP-L3 Is most useful in detection of recurrence of hepatocellular carcinoma in patients after tumor ablation and with low AFP level. Viruses-Basel 14:10. https://doi.org/10.3390/v14040775

    Article  Google Scholar 

  8. Pang BY, Leng Y, Wang XL, Wang YQ, Jiang LH (2023) A meta-analysis and of clinical values of 11 blood biomarkers, such as AFP, DCP, and GP73 for diagnosis of hepatocellular carcinoma. Ann Med 55:42–61. https://doi.org/10.1080/07853890.2022.2153163

    Article  CAS  PubMed  Google Scholar 

  9. Schepers EJ, Glaser K, Zwolshen HM, Hartman SJ, Bondoc AJ (2023) Structural and functional impact of posttranslational modification of glypican-3 on liver carcinogenesis. Cancer Res 83:1933–1940. https://doi.org/10.1158/0008-5472.Can-22-3895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Grega SD, Zheng DX, Zheng Q-H (2022) Imaging ligands targeting glypican-3 receptor expression in hepatocellular carcinoma. Am J Nucl Med Mol Imaging 12:113–121

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Tahon AM, El-Ghanam MZ, Zaky S, Emran TM, Bersy AM, El-Raey F, Az E, El Kharsawy AM, Johar D (2019) Significance of Glypican-3 in early detection of hepatocellular carcinoma in cirrhotic patients. J Gastrointest Canc. 50(3):434–441. https://doi.org/10.1007/s12029-018-0095-2

    Article  CAS  Google Scholar 

  12. Yildirim HC, Kavgaci G, Chalabiyev E, Dizdar O (2023) Advances in the early detection of hepatobiliary cancers. Cancers 15:16. https://doi.org/10.3390/cancers15153880

    Article  CAS  Google Scholar 

  13. Al-Shami A, Oweis RJ, Al-Fandi MG (2021) Developing an electrochemical immunosensor for early diagnosis of hepatocellular carcinoma. Sens Rev 41:125–134. https://doi.org/10.1108/SR-02-2020-0030

    Article  Google Scholar 

  14. Jiang C, Cai YQ, Yang JJ, Ma CY, Chen JX, Huang L, Xiang Z, Wu J (2023) Radiomics in the diagnosis and treatment of hepatocellular carcinoma. Hepatob Pancreatic Dis Int 22:346–351. https://doi.org/10.1016/j.hbpd.2023.03.010

    Article  CAS  Google Scholar 

  15. You B, Assenat E, Payen L, Mazard T, Glehen O, Calattini S, Villeneuve L, Lescuyer G, Vire B, Ychou M (2022) hPG80 and cancer: a new blood biomarker in development for patient monitoring. Bull Cancer 109:707–713. https://doi.org/10.1016/j.bulcan.2022.03.009

    Article  PubMed  Google Scholar 

  16. Lu WX, Xie XX, Lan XL, Wu P, Peng HM, He J, Zhong LP, Liu XY, Deng ZM, Tan ZK, Wu AQ, Shi L, Huang Y (2023) An electrochemical immunosensor for the detection of Glypican-3 based on enzymatic ferrocene-tyramine deposition reaction. Biosens Bioelectron 225:10. https://doi.org/10.1016/j.bios.2023.115081

    Article  CAS  Google Scholar 

  17. Li GY, Wang B, Zhao L, Shi XH, Wu GX, Chen W, Sun LX, Liang JT, Zhou ZD (2022) Label-free detection of glypican-3 using reduced graphene oxide /polyetherimide/gold nanoparticles enhanced aptamer specific sensing interface on light-addressable potentiometric sensor. Electrochim Acta 426:11. https://doi.org/10.1016/j.electacta.2022.140808

    Article  CAS  Google Scholar 

  18. Radi A, Abd-Ellatief MR (2021) Electrochemical aptasensors: current status and future perspectives. Diagnostics 11:33. https://doi.org/10.3390/diagnostics11010104

    Article  CAS  Google Scholar 

  19. Wu SM, Liang Y, Xu Y, Tong YY, Chen Y, Chen XL (2022) Graphene-based electrochemical sensor for detection of hepatocellular carcinoma markers. Front Chem 10:6. https://doi.org/10.3389/fchem.2022.883627

    Article  CAS  Google Scholar 

  20. Rahn KL, Peramune U, Zhang TY, Anand RK (2023) Label-Free electrochemical methods for disease detection. Annu Rev Anal Chem 16:49–69. https://doi.org/10.1146/annurev-anchem-091622-085754

    Article  CAS  Google Scholar 

  21. Shi XH, Chen M, Feng HF, Zhou ZD, Wu RQ, Li WZ, Liang JT, Chen JJ, Li GY (2021) Glypican-3 electrochemical aptasensor based on reduced graphene oxide-chitosan-ferrocene deposition of platinum-palladium bimetallic nanoparticles. J Appl Electrochem 51:781–794. https://doi.org/10.1007/s10800-021-01534-4

    Article  CAS  Google Scholar 

  22. Zhou H, Du X, Zhang ZG (2021) Electrochemical sensors for detection of markers on tumor cells. Int J Hydrog Energy 22:15. https://doi.org/10.3390/ijms22158184

    Article  CAS  Google Scholar 

  23. Abedi R, Raoof JB, Mohseni M, Bagheri Hashkavayi A (2024) Sandwich-type electrochemical aptasensor based on hemin-graphite oxide as a signal label and rGO/MWCNTs/chitosan/carbon quantum dot modified electrode for sensitive detection of Acinetobacter baumannii bacteria. Anal Chim Acta 1303:342491. https://doi.org/10.1016/j.aca.2024.342491

    Article  CAS  PubMed  Google Scholar 

  24. Zhang WX, Xiao GC, Chen J, Wang L, Hu QZ, Wu J, Zhang WH, Song M, Qiao JW, Xu CH (2021) Electrochemical biosensors for measurement of colorectal cancer biomarkers. Anal Bioanal Chem 413:2407–2428. https://doi.org/10.1007/s00216-021-03197-8

    Article  CAS  PubMed  Google Scholar 

  25. Kim JH, Suh YJ, Park D, Yim H, Kim H, Kim HJ, Yoon DS, Hwang KS (2021) Technological advances in electrochemical biosensors for the detection of disease biomarkers, Biomed. Eng Lett 11:309–334. https://doi.org/10.1007/s13534-021-00204-w

    Article  Google Scholar 

  26. Liu FP, Geng LG, Ye FG, Zhao SL (2022) MOF-derivated MnO@C nanocomposite with bidirectional electrocatalytic ability as signal amplification for dual-signal electrochemical sensing of cancer biomarker. Talanta 239:10. https://doi.org/10.1016/j.talanta.2021.123150

    Article  CAS  Google Scholar 

  27. Chen HA, Li YY, Song YC, Liu FJ, Deng DM, Zhu XL, He HB, Yan XX, Luo LQ (2023) A sandwich-type electrochemical immunosensor based on spherical nucleic acids-templated Ag nanoclusters for ultrasensitive detection of tumor biomarker. Biosens Bioelectron 223:8. https://doi.org/10.1016/j.bios.2022.115029

    Article  CAS  Google Scholar 

  28. Li GY, Chen M, Wang B, Wang CX, Wu GX, Liang JT, Zhou ZD (2022) Dual-signal sandwich-type aptasensor based on H-rGO-Mn3O4 nanozymes for ultrasensitive Golgi protein 73 determinationAnal. Chim Acta 1221:11. https://doi.org/10.1016/j.aca.2022.340102

    Article  CAS  Google Scholar 

  29. Bai HY, del Campo FJ, Tsai YC (2014) Scanning electrochemical microscopy for study of aptamer-thrombin interfacial interactions on gold disk microelectrodes. J Colloid Interface Sci 417:333–335. https://doi.org/10.1016/j.jcis.2013.11.050

    Article  CAS  PubMed  Google Scholar 

  30. Yari A, Fathabad SH (2020) A high-performance supercapacitor based on cerium molybdate nanoparticles anchored on N, P co-doped reduced graphene oxide nanocomposite as the electrode. J Mater Sci - Mater Electron 31:13051–13062. https://doi.org/10.1007/s10854-020-03855-0

    Article  CAS  Google Scholar 

  31. Orzari LO, Silva LRGE, de Freitas RC, Brazaca LC, Janegitz BC (2024) Lab-made disposable screen-printed electrochemical sensors and immunosensors modified with Pd nanoparticles for Parkinson’s disease diagnostics. Mikrochim Acta 191:76. https://doi.org/10.1007/s00604-023-06158-3

    Article  CAS  PubMed  Google Scholar 

  32. da Silva AD, Paschoalino WJ, Damasceno JPV, Kubota LT (2020) Structure, properties, and electrochemical sensing applications of graphene-based materials. ChemElectroChem 7:4508–4525. https://doi.org/10.1002/celc.202001168

    Article  CAS  Google Scholar 

  33. Zhou NF, Luo G, Qin W, Wu C, Jia CK (2023) One-pot synthesis of boron-doped cobalt oxide nanorod coupled with reduced graphene oxide for sodium ion batteries. J Colloid Interface Sci 640:710–718. https://doi.org/10.1016/j.jcis.2023.03.028

    Article  CAS  PubMed  Google Scholar 

  34. Reynoso-Soto EA, Félix-Navarro RM, Rivera-Lugo YY, Lozano-Garcia A, Dominguez-Vargas DA, Silva-Carrillo C (2022) Electrochemical determination of glucose using nitrogen-doped graphene. Top Catal 65:1235–1243. https://doi.org/10.1007/s11244-022-01658-7

    Article  CAS  Google Scholar 

  35. Bi LL, Teng Y, Baghayeri M, Bao JL (2023) Employing Pd nanoparticles decorated on halloysite nanotube/carbon composite for electrochemical aptasensing of HER2 in breast cancer patients. Environ Res 237:7. https://doi.org/10.1016/j.envres.2023.117030

    Article  CAS  Google Scholar 

  36. Zhao P, Chen S, Liang Y, Chen YY, Lan P, Huo DQ, Hou CJ (2022) Metalloporphyrin hemin modified carbon nanotube decorated titanium carbide with redox catalytic ability for electrochemical determination of hydrogen peroxide and uric acid. J Colloid Interface Sci 628:456–466. https://doi.org/10.1016/j.jcis.2022.07.190

    Article  CAS  PubMed  Google Scholar 

  37. Wang GX, Wang JM, Qi YQ, Wang M (2020) Controllable direct electrochemical and catalytic activity of hemin-quadruplex complexes. J Electroanal Chem 878:5. https://doi.org/10.1016/j.jelechem.2020.114451

    Article  CAS  Google Scholar 

  38. Zhou SY, Sun HM, Wang XF, Lu P, Huo DQ, Li JW, Luo XG, Hou CJ (2021) Fe-hemin-metal organic frameworks/three-dimensional graphene composites with efficient peroxidase-like bioactivity for real-time electrochemical detection of extracellular hydrogen peroxide. J Electrochem Soc 168:9. https://doi.org/10.1149/1945-7111/ac3b04

    Article  CAS  Google Scholar 

  39. Li SN, Li XH, Cao LP, Wang CX, Liang JT, Zhou ZD, Li GY (2022) An ultrasensitive glypican-3 electrochemical aptasensor based on reduced graphene oxide-carboxymethylchitosan-hemin/palladium nanoparticlesJ. Electrochem Soc 169:10. https://doi.org/10.1149/1945-7111/ac8955

    Article  CAS  Google Scholar 

  40. Roy S, Nagabooshanam S, Wadhwa S, Chauhan N, Mathur A, Khan SA, Davis J (2020) Ultra-sensitive detection of L-tyrosine using molecularly imprinted electrochemical sensor towards diabetic foot ulcer detection. Electrochem commun 117:5. https://doi.org/10.1016/j.elecom.2020.106782

    Article  CAS  Google Scholar 

  41. Boateng E, Dondapati JS, Thiruppathi AR, Chen AC (2020) Significant enhancement of the electrochemical hydrogen uptake of reduced graphene oxide via boron-doping and decoration with Pd nanoparticles. Int J Hydrog Energy 45:28951–28963. https://doi.org/10.1016/j.ijhydene.2020.07.128

    Article  CAS  Google Scholar 

  42. Zhou ZD, Zhao L, Li WZ, Chen M, Feng HF, Shi XH, Liang JT, Li GY (2020) Glypican-3 electrochemical aptamer nanobiosensor based on hemin/graphene nanohybrids peroxidase-like catalytic silver deposition. Mikrochim Acta 187:11. https://doi.org/10.1007/s00604-020-04284-w

    Article  CAS  Google Scholar 

  43. Li G, Feng H, Shi X, Chen M, Liang J, Zhou Z (2021) Highly sensitive electrochemical aptasensor for Glypican-3 based on reduced graphene oxide-hemin nanocomposites modified on screen-printed electrode surface, Bioelectrochemistry. 138(2021). https://doi.org/10.1016/j.bioelechem.2020.107696

  44. Rho D, Kim S (2021) Demonstration of a label-free and low-cost optical cavity-based biosensor using streptavidin and C-reactive protein. Biosensors-Basel 11:13. https://doi.org/10.3390/bios11010004

    Article  CAS  Google Scholar 

  45. Zhang X, Li HY, Li W, Liang HP, Ding ZH, Xu L, Zhang Y, Xu XX, Li CY, Li HY, Wang YY (2023) High-performance assaying phosphatidylinositol proteoglycan 3 based on a dual-mode biosensor coupling near-infrared photoelectrochemical with ratiometric electrochemical sensing. Sens Actuators B Chem 381:10. https://doi.org/10.1016/j.snb.2023.133419

    Article  CAS  Google Scholar 

  46. Chen JJ, Xie CM, Wang CR, Wan Y, Dong ZN, Li M, Xu WW (2017) Development of a time-resolved fluorescence immunoassay for the diagnosis of hepatocellular carcinoma based on the detection of glypican-3. J Fluoresc 27:1479–1485. https://doi.org/10.1007/s10895-017-2087-1

    Article  CAS  PubMed  Google Scholar 

  47. Yu S, Li ZF, Li JZ, Zhao SM, Wu SG, Liu HJ, Bi XJ, Li DY, Dong JX, Duan SL, Hammock BD (2021) Generation of dual functional nanobody-nanoluciferase fusion and its potential in bioluminescence enzyme immunoassay for trace glypican-3 in serum. Sens Actuators B Chem 336:9. https://doi.org/10.1016/j.snb.2021.129717

    Article  CAS  Google Scholar 

  48. Li GY, Chen W, Mi DH, Wang B, Li HM, Wu GX, Ding P, Liang JT, Zhou ZD (2022) A highly sensitive strategy for glypican-3 detection based on aptamer/gold carbon dots/magnetic graphene oxide nanosheets as fluorescent biosensor. Anal Bioanal Chem 414:6441–6453. https://doi.org/10.1007/s00216-022-04201-5

    Article  CAS  PubMed  Google Scholar 

  49. Xie CM, Tiede C, Zhang XY, Wang CR, Li ZX, Xu X, McPherson MJ, Tomlinson DC, Xu WW (2017) Development of an affimerantibody combined immunological diagnosis kit for glypican-3. Sci Rep 7:9. https://doi.org/10.1038/s41598-017-10083-w

    Article  Google Scholar 

  50. Chen M, Li HM, Su XM, Wu RQ, Feng HF, Shi XH, Liang JT, Chen JJ, Li GY (2021) Label-free electrochemical aptasensor based on reduced graphene oxide-hemin-chitosan nanocomposite for the determination of glypican-3. New J Chem 45:8608–8618. https://doi.org/10.1039/d1nj00633a

    Article  CAS  Google Scholar 

  51. Li GY, Feng HF, Shi XH, Chen M, Liang JT, Zhou ZD (2021) Highly sensitive electrochemical aptasensor for Glypican-3 based on reduced graphene oxide-hemin nanocomposites modified on screen-printed electrode surface. Bioelectrochemistry 138:12. https://doi.org/10.1016/j.bioelechem.2020.107696

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Nature Science Foundation of China (Nos. 62371143 and 62261010), the Major Projects of Guangxi Science and Technology (No. GuikeAA24999003), and the Projects of Talents Recruitment of GDUPT in Guangdong Province (RC-XJ2022000401).

Author information

Authors and Affiliations

  1. College of Chemistry, Guangdong University of Petrochemical Technology, Guandu Road, Maoming, Guangdong, 525000, People’s Republic of China

    Guiyin Li & Bingbing Wan

  2. School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin, Guangxi, 541004, People’s Republic of China

    Guiyin Li, Fei Guo, Jianlu Liang, Bingbing Wan, Jintao Liang & Zhide Zhou

Authors
  1. Guiyin Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Fei Guo
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Jianlu Liang
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Bingbing Wan
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Jintao Liang
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Zhide Zhou
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding authors

Correspondence to Jintao Liang or Zhide Zhou.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

The human serum samples used in this study were approved by the Guangxi Key Laboratory of Metabolic Diseases Research Ethics Committee in Guilin, China.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The authors guarantee that the work is an original work because it has never been published before and has not been submitted to other places for publication.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, G., Guo, F., Liang, J. et al. Sandwich-type supersensitive electrochemical aptasensor of glypican-3 based on PrGO-Hemin-PdNP and AuNP@PoPD. Microchim Acta 191, 340 (2024). https://doi.org/10.1007/s00604-024-06419-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-024-06419-9

Keywords