Skip to main content
Log in

Reversible capturing and voltammetric determination of circulating tumor cells using two-dimensional nanozyme based on PdMo decorated with gold nanoparticles and aptamer

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

Abstract

A novel cytosensor was constructed for the ultrasensitive detection and nondestructive release of circulating tumor cells (CTCs) by combining Au nanoparticles-loaded two-dimensional bimetallic PdMo (2D Au@PdMo) nanozymes and electrochemical reductive desorption. The 2D Au@PdMo nanozymes possessed high-efficiency peroxidase-like activity and were assembled with an aptamer composed of a thiol-modified epithelial specific cell adhesion molecule (EpCAM) to strengthen CTCs adhesion. Moreover, the electrode surface was decorated with highly fractal Au nanostructures (HFAuNSs) composites due to the similarity in fractal nanostructure with the CTCs membrane to enhance the CTCs anchoring efficiency and release capability. The captured CTCs could be further efficiently dissociated and nondestructively released from the modified electrodes upon electrochemical reductive desorption. The designed cytosensor showed an excellent analytical performance, with a wide linear range from 2 to 1 × 105 cells mL−1 and low limit of detection (LOD) of 2 cells mL−1 (S/N = 3) at the working potential in the range  −0.6 to 0.2 V. A satisfactory CTCs release reaching a range of 93.7–97.4% with acceptable RSD from 3.55 to 6.41% and good cell viability was obtained. Thus, the developed cytosensor might provide a potential alternative to perform CTC-based liquid biopsies, with promising applications in early diagnosis of tumors.

Graphical abstract

Preparation and mechanism of desorption of the cytosensor based on 2D Au@PdMo nanozymes and electrochemical reductive desorption for the detection and release of CTCs. A Preparation procedure of the Apt/Au@PbMo bioconjugates. B Fabrication process of the sandwich-type cytosensor. C Electrochemical signal produced by the Au@PdMo nanozymes. D Mechanism of electrochemical reductive desorption for CTCs release

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jackson JM, Witek MA, Kamande JW, Soper SA (2017) Materials and microfluidics: enabling the efficient isolation and analysis of circulating tumour cells. Chem Soc Rev 46(14):4245–4280. https://doi.org/10.1039/C7CS00016B

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kilgour E, Rothwell DG, Brady G, Dive C (2020) Liquid biopsy-based biomarkers of treatment response and resistance. Cancer Cell 37(4):485–495. https://doi.org/10.1016/j.ccell.2020.03.012

    Article  CAS  PubMed  Google Scholar 

  3. Pantel K, Alix-Panabieres C (2019) Liquid biopsy and minimal residual disease - latest advances and implications for cure. Nat Rev Clin Oncol 16(7):409–424. https://doi.org/10.1038/s41571-019-0187-3

    Article  CAS  PubMed  Google Scholar 

  4. Lin M, Chen JF, Lu YT, Zhang Y, Song J, Hou S, Ke Z, Tseng HR (2014) Nanostructure embedded microchips for detection, isolation, and characterization of circulating tumor cells. Acc Chem Res 47:2941–2950. https://doi.org/10.1021/ar5001617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Parkinson D, Dracopoli N, Petty B, Compton C, Cristofanilli M, Deisseroth A, Hayes D, Kapke G, Kumar P, Lee J, Liu M, McCormack R, Mikulski S, Nagahara L, Pantel K, Pearson-White S, Punnoose E, Roadcap L, Schade A, Scher H, Sigman C, Kelloff G (2012) Considerations in the development of circulating tumor cell technology for clinical use. J Transl Med 10:138. https://doi.org/10.1186/1479-5876-10-138

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chemi F, Rothwell DG, McGranahan N, Gulati S, Abbosh C, Pearce SP, Zhou C, Wilson GA, Jamal-Hanjani M, Birkbak N, Pierce J, Kim CS, Ferdous S, Burt DJ, Slane-Tan D, Gomes F, Moore D, Shah R, Al Bakir M, Hiley C, Veeriah S, Summers Y, Crosbie P, Ward S, Mesquita B, Dynowski M, Biswas D, Tugwood J, Blackhall F, Miller C, Hackshaw A, Brady G, Swanton C, Dive C, Consortium TR (2019) Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse. Nat Med 25(10):1534–1539. https://doi.org/10.1038/s41591-019-0593-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, Dotson WD, Douglas MP, Berg AO, Group EW (2009) The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative: methods of the EGAPP working group. Genet Med 11(1):3–14. https://doi.org/10.1097/GIM.0b013e318184137c

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhou X, Li Y, Wu H, Huang W, Ju H, Ding S (2019) A amperometric immunosensor for sensitive detection of circulating tumor cells using a tyramide signal amplification-based signal enhancement system. Biosens Bioelectron 130:88–94. https://doi.org/10.1016/j.bios.2019.01.023

    Article  CAS  PubMed  Google Scholar 

  9. Wu J, Wang X, Wang Q, Lou Z, Li S, Zhu Y, Qin L, Wei H (2019) Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II). Chem Soc Rev 48(4):1004–1076. https://doi.org/10.1039/c8cs00457a

    Article  CAS  PubMed  Google Scholar 

  10. Wei H, Wang EK (2013) Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chem Soc Rev 42:6060–6093. https://doi.org/10.1039/c3cs35486e

    Article  CAS  PubMed  Google Scholar 

  11. Campuzano S, Pedrero M, Yáñez-Sedeño P, Pingarrón JJ (2020) Nanozymes in electrochemical affinity biosensing. Mikrochim Acta 187:423. https://doi.org/10.1007/s00604-020-04390-9

    Article  CAS  PubMed  Google Scholar 

  12. Liang M, Wang Y, Ma K, Yu S, Chen Y, Deng Z, Liu Y, Wang F (2020) Engineering inorganic nanoflares with elaborate enzymatic specificity and efficiency for versatile biofilm eradication. Small 16:e2002348. https://doi.org/10.1002/smll.202002348

    Article  CAS  PubMed  Google Scholar 

  13. Li X, Li X, Li D, Zhao M, Wu H, Shen B, Liu P, Ding SJ (2020) Electrochemical biosensor for ultrasensitive exosomal miRNA analysis by cascade primer exchange reaction and MOF@Pt@MOF nanozyme. Biosens Bioelectron 168:112554. https://doi.org/10.1016/j.bios.2020.112554

    Article  CAS  PubMed  Google Scholar 

  14. Gao L, Zhuang J, Nie L, Zhang J, Zhang Y, Gu N, Wang T, Feng J, Yang D, Perrett S, Yan XY (2007) Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat Nanotechnol 2:577–583. https://doi.org/10.1038/nnano.2007.260

    Article  CAS  PubMed  Google Scholar 

  15. Liu W, Guo J, Chen C, Ni P, Jiang Y, Zhang C, Wang B, Lu YZ (2021) Ultrathin PdCu alloy nanosheet-assembled 3D nanoflowers with high peroxidase-like activity toward colorimetric glucose detection. Mikrochim Acta 188:114. https://doi.org/10.1007/s00604-021-04776-3

    Article  CAS  PubMed  Google Scholar 

  16. Liu X, Yan Z, Zhang Y, Liu Z, Sun Y, Ren J, Qu X (2019) Two-dimensional metal-organic framework/enzyme hybrid nanocatalyst as a benign and self-activated cascade reagent for in vivo wound healing. ACS Nano 13(5):5222–5230. https://doi.org/10.1021/acsnano.8b09501

    Article  CAS  PubMed  Google Scholar 

  17. Mu J, He L, Fan W, Tang W, Wang Z, Jiang C, Zhang D, Liu Y, Deng H, Zou J, Jacobson O, Qu J, Huang P, Chen X (2020) Cascade reactions catalyzed by planar metal-organic framework hybrid architecture for combined cancer therapy. Small 16(42):e2004016. https://doi.org/10.1002/smll.202004016

    Article  CAS  PubMed  Google Scholar 

  18. You J, Liu L, Huang W, Manners I, Dou HJ (2021) In situ redox-active micelle-based reaction platforms for preparation of noble metal nanocomposites with photothermal conversion capability. ACS Appl Mater Interfaces 13:13648–13657. https://doi.org/10.1021/acsami.0c21925

    Article  CAS  PubMed  Google Scholar 

  19. Zhang H, Liang F, Wu X, Liu Y, Chen A (2020) Recognition and sensitive detection of CTCs using a controllable label-free electrochemical cytosensor. Mikrochim Acta 187:487. https://doi.org/10.1007/s00604-020-04452-y

    Article  CAS  PubMed  Google Scholar 

  20. Wang H, Wan K, Shi X (2019) Recent advances in nanozyme research. Adv Mater 31:e1805368. https://doi.org/10.1002/adma.201805368

    Article  CAS  PubMed  Google Scholar 

  21. Feng L, Zhang L, Zhang S, Chen X, Li P, Gao Y, Xie S, Zhang A, Wang H (2020) Plasma-assisted controllable doping of nitrogen into MoS nanosheets as efficient nanozymes with enhanced peroxidase-like catalysis activity. ACS Appl Mater Interfaces 12:17547–17556. https://doi.org/10.1021/acsami.0c01789

    Article  CAS  PubMed  Google Scholar 

  22. Zhou X, Luo B, Kang K, Zhang Y, Jiang P, Lan F, Yi Q, Wu Y (2019) Leukocyte-repelling biomimetic immunomagnetic nanoplatform for high-performance circulating tumor cells isolation. Small 15(17):e1900558. https://doi.org/10.1002/smll.201900558

    Article  CAS  PubMed  Google Scholar 

  23. Yan S, Chen P, Zeng X, Zhang X, Li Y, Xia Y, Wang J, Dai X, Feng X, Du W, Liu BF (2017) Integrated multifunctional electrochemistry microchip for highly efficient capture, release, lysis, and analysis of circulating tumor cells. Anal Chem 89:12039–12044. https://doi.org/10.1021/acs.analchem.7b02469

    Article  CAS  PubMed  Google Scholar 

  24. Dong J, Chen JF, Smalley M, Zhao M, Ke Z, Zhu Y, Tseng HR (2020) Nanostructured substrates for detection and characterization of circulating rare cells: from materials research to clinical applications. Adv Mater 32:e1903663. https://doi.org/10.1002/adma.201903663

    Article  CAS  PubMed  Google Scholar 

  25. Shen H, Deng W, He Y, Li X, Song J, Liu R, Liu H, Yang G, Li L (2020) Ultrasensitive aptasensor for isolation and detection of circulating tumor cells based on CeO2@Ir nanorods and DNA walker. Biosens Bioelectron 168:112516. https://doi.org/10.1016/j.bios.2020.112516

    Article  CAS  PubMed  Google Scholar 

  26. Zhu L, Feng X, Yang S, Wang J, Pan Y, Ding J, Li C, Yin X, Yu Y (2021) Colorimetric detection of immunomagnetically captured rare number CTCs using mDNA-wrapped single-walled carbon nanotubes. Biosens Bioelectron 172:112780. https://doi.org/10.1016/j.bios.2020.112780

    Article  CAS  PubMed  Google Scholar 

  27. Zhang M, Zhai Q, Wan L, Chen L, Peng Y, Deng C, Xiang J, Yan JW (2018) Electrochemical impedance spectroscopy for real-time detection of lipid membrane damage based on a porous self-assembly monolayer support. Anal Chem 90:7422–7427. https://doi.org/10.1021/acs.analchem.8b00884

    Article  CAS  PubMed  Google Scholar 

  28. Dokukin M, Guz N, Gaikwad R, Woodworth C, Sokolov I (2011) Cell surface as a fractal: normal and cancerous cervical cells demonstrate different fractal behavior of surface adhesion maps at the nanoscale. Phys Rev Lett 107:028101. https://doi.org/10.1103/PhysRevLett.107.028101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang P, Chen L, Xu T, Liu H, Liu X, Meng J, Yang G, Jiang L, Wang S (2013) Programmable fractal nanostructured interfaces for specific recognition and electrochemical release of cancer cells. Adv Mater 25:3566–3570. https://doi.org/10.1002/adma.201300888

    Article  CAS  PubMed  Google Scholar 

  30. Luo M, Zhao Z, Zhang Y, Sun Y, Xing Y, Lv F, Yang Y, Zhang X, Hwang S, Qin Y, Ma JY, Lin F, Su D, Lu G, Guo S (2019) PdMo bimetallene for oxygen reduction catalysis. Nature 574(7776):81–85. https://doi.org/10.1038/s41586-019-1603-7

    Article  CAS  PubMed  Google Scholar 

  31. Chen J, Zhang J, Yang H, Fu F, Chen G (2010) A strategy for development of electrochemical DNA biosensor based on site-specific DNA cleavage of restriction endonuclease. Biosens Bioelectron 26:144–148. https://doi.org/10.1016/j.bios.2010.05.033

    Article  CAS  PubMed  Google Scholar 

  32. Han D, Yan Y, Wang J, Zhao M, Duan X, Kong L, Wu H, Cheng W, Min X, Ding S (2019) An enzyme-free electrochemiluminesce aptasensor for the rapid detection of Staphylococcus aureus by the quenching effect of MoS2-PtNPs-vancomycin to S2O82−/O2 system. Sensors Actuators B Chem 288:586–593. https://doi.org/10.1016/j.snb.2019.03.050

    Article  CAS  Google Scholar 

  33. Pan D, Fang Z, Yang E, Ning Z, Zhou Q, Chen K, Zheng Y, Zhang Y, Shen YF (2020) Facile preparation of WO3-x dots with remarkably low toxicity and uncompromised activity as co-reactants for clinical diagnosis by electrochemiluminescence. Angew Chem Int Ed Eng 59(38):16747–16754. https://doi.org/10.1002/anie.202007451

    Article  CAS  Google Scholar 

  34. Cao Y, Zhu W, Wei H, Ma C, Lin Y, Zhu JJ (2020) Stable and monochromatic all-inorganic halide perovskite assisted by hollow carbon nitride nanosphere for ratiometric electrochemiluminescence bioanalysis. Anal Chem 92(5):4123–4130. https://doi.org/10.1021/acs.analchem.0c00070

    Article  CAS  PubMed  Google Scholar 

  35. Gu C, Guo C, Li Z, Wang M, Zhou N, He L, Zhang Z, Du M (2019) Bimetallic ZrHf-based metal-organic framework embedded with carbon dots: ultra-sensitive platform for early diagnosis of HER2 and HER2-overexpressed living cancer cells. Biosens Bioelectron 134:8–15. https://doi.org/10.1016/j.bios.2019.03.043

    Article  CAS  PubMed  Google Scholar 

  36. Hashemi P, Afkhami A, Baradaran B, Halabian R, Madrakian T, Arduini F, Nguyen T, Bagheri H (2020) Well-orientation strategy for direct immobilization of antibodies: development of the immunosensor using the boronic acid-modified magnetic graphene nanoribbons for ultrasensitive detection of lymphoma cancer cells. Anal Chem 92(16):11405–11412. https://doi.org/10.1021/acs.analchem.0c02357

    Article  CAS  PubMed  Google Scholar 

  37. Wang H, Zhou C, Sun X, Jian Y, Kong Q, Cui K, Ge S, Yu JH (2018) Polyhedral-AuPd nanoparticles-based dual-mode cytosensor with turn on enable signal for highly sensitive cell evalution on lab-on-paper device. Biosens Bioelectron 117:651–658. https://doi.org/10.1016/j.bios.2018.07.004

    Article  CAS  PubMed  Google Scholar 

  38. Peng Y, Pan Y, Han Y, Sun Z, Jalalah M, Al-Assiri M, Harraz F, Yang J, Li G (2020) Direct analysis of rare circulating tumor cells in whole blood based on their controlled capture and release on electrode surface. Anal Chem 92(19):13478–13484. https://doi.org/10.1021/acs.analchem.0c02906

    Article  CAS  PubMed  Google Scholar 

  39. Peng Y, Peng Y, Tang S, Shen H, Sheng S, Wang Y, Wang T, Cai J, Xie G, Feng W (2020) PdIrBP mesoporous nanospheres combined with superconductive carbon black for the electrochemical determination and collection of circulating tumor cells. Mikrochim Acta 187(4):216. https://doi.org/10.1007/s00604-020-4213-z

    Article  CAS  PubMed  Google Scholar 

  40. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP (2017) The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 67(2):93–99. https://doi.org/10.3322/caac.21388

    Article  PubMed  Google Scholar 

Download references

Funding

This research was funded by the financial support from the National Science and Technology Major Project of the Ministry of Science and Technology of China (2018ZX10732202), the National Natural Science Foundation of China (81873980), the Natural Science Foundation Project of Chongqing (cstc2018jcyjAX0349), and the Zhejiang Provincial Natural Science Fund (LQ21H200005).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yurong Yan or Shijia Ding.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

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

Supplementary information

ESM 1

(DOCX 4896 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, W., Fan, L., Guo, Z. et al. Reversible capturing and voltammetric determination of circulating tumor cells using two-dimensional nanozyme based on PdMo decorated with gold nanoparticles and aptamer. Microchim Acta 188, 319 (2021). https://doi.org/10.1007/s00604-021-04927-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00604-021-04927-6

Keywords

Navigation