Skip to main content

Advertisement

Log in

Hairpin oligosensor using SiQDs: Förster resonance energy transfer study and application for miRNA-21 detection

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

MicroRNAs are known to be tumor suppressors and promoters and can be used as cancer markers. In this work, a novel oligosensor was designed using Si quantum dots (SiQDs) for the detection of miRNAs. Five-nanometer SiQDs were synthesized, with a band gap of 2.8 eV, fluorescence lifetime of 4.56 μs (τ1/2 = 3.26 μs), quantum yield of 25%, fluorescence rate constant of 6.25 × 104, and non-radiative rate constant of 1.60 × 105 s−1. They showed excellent water dispersibility, good stability (with 95% confidence for 6-month storage) without photobleaching, and high biocompatibility, with an IC50 value of 292.2 μg/L. The SiQDs and Black Hole Quencher-1 (BHQ1) were conjugated to the 5′ and 3′ terminals of an oligomer, respectively. The resulting hairpin molecular beacon showed resonance energy transfer efficiency of 63%. A distance of 0.91 R (Förster distance) between SiQD and BHQ1 was obtained. In the presence of a stoichiometric amount of the complementary oligonucleotide (ΔGhybridization = −35.09 kcal mol−1), 98% of the fluorescence was recovered due to loop opening of the hairpin structure. The probe showed good selectivity toward miRNA-21, with a limit of detection of 14.9 fM. The oligosensor recoveries of miRNA-21 spiked in human serum and urine were 94–98% and 93–108%, respectively.

Graphical abstract

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

Access this article

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Scheme 1
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Wu Y, Sarkissyan M, Vadgama J. Epithelial-mesenchymal transition and breast cancer. J Clin Med. 2016;5(2):13.

    Article  PubMed Central  Google Scholar 

  2. Cardoso AR, Moreira FTC, Fernandes R, Sales MGF. Novel and simple electrochemical biosensor monitoring attomolar levels of miRNA-155 in breast cancer. Biosens Bioelectron. 2016;80:621–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Spanhol FA, Oliveira LS, Petitjean C, Heutte L. A dataset for breast cancer histopathological image classification. IEEE Trans Biomed Eng. 2016;63(7):1455–62.

    Article  PubMed  Google Scholar 

  4. Huzarski T, Górecka-Szyld B, Huzarska J, Psut-Muszyńska G, Wilk G, Sibilski R, et al. Screening with magnetic resonance imaging, mammography and ultrasound in women at average and intermediate risk of breast cancer. Hered Cancer Clin Pract. 2017;15(1):4.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Pavithra P, Ravichandran K, Sekar K, Manikandan R. The effect of thermography on breast Cancer detection. Syst Rev Pharm. 2018;9(1):10–6.

    Article  Google Scholar 

  6. Arif S, Qudsia S, Urooj S, Chaudry N, Arshad A, Andleeb S. Blueprint of quartz crystal microbalance biosensor for early detection of breast cancer through salivary autoantibodies against ATP6AP1. Biosens Bioelectron. 2015;65:62–70.

    Article  CAS  PubMed  Google Scholar 

  7. Khakbaz F, Mahani M. Micro-RNA detection based on fluorescence resonance energy transfer of DNA-carbon quantum dots probes. Anal Biochem. 2017;523:32–8.

    Article  CAS  PubMed  Google Scholar 

  8. Khoshroo A, Mazloum-Ardakani M, Forat-Yazdi M. Enhanced performance of label-free electrochemical immunosensor for carbohydrate antigen 15-3 based on catalytic activity of cobalt sulfide/graphene nanocomposite. Sens Actuators B Chem. 2018;255:580–7.

    Article  CAS  Google Scholar 

  9. Ke H, Zhang X, Huang C, Jia N. Electrochemiluminescence evaluation for carbohydrate antigen 15-3 based on the dual-amplification of ferrocene derivative and Pt/BSA core/shell nanospheres. Biosens Bioelectron. 2018;103:62–8.

    Article  CAS  PubMed  Google Scholar 

  10. Ermini ML, Chadtova Song X, Springer T, Homola J. Peptide functionalization of gold nanoparticles for the detection of carcinoembryonic antigen in blood plasma via SPR-based biosensor. Front Chem. 2019;7:40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gu X, She Z, Ma T, Tian S, Kraatz H-B. Electrochemical detection of carcinoembryonic antigen. Biosens Bioelectron. 2018;102:610–6.

    Article  CAS  PubMed  Google Scholar 

  12. Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, et al. Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One. 2012;7(10):e47003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294(5543):853–8.

    Article  CAS  PubMed  Google Scholar 

  14. Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350.

    Article  CAS  PubMed  Google Scholar 

  15. Deng D, Liu Z, Du Y. Epigenetic alterations as cancer diagnostic, prognostic, and predictive biomarkers. Advances in genetics. 71: Elsevier; 2010. p. 125–76.

  16. Grady WM, Tewari M. The next thing in prognostic molecular markers: microRNA signatures of cancer. Gut. 2010;59(6):706–8.

    Article  CAS  PubMed  Google Scholar 

  17. Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141(5):672–5.

    Article  PubMed  Google Scholar 

  18. Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol. 2010;119(3):586–93.

    Article  CAS  PubMed  Google Scholar 

  19. Zhang HL, Yang LF, Zhu Y, Yao XD, Zhang SL, Dai B, et al. Serum miRNA-21: elevated levels in patients with metastatic hormone-refractory prostate cancer and potential predictive factor for the efficacy of docetaxel-based chemotherapy. Prostate. 2011;71(3):326–31.

    Article  CAS  PubMed  Google Scholar 

  20. Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA. 2005;11(3):241–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lodes MJ, Caraballo M, Suciu D, Munro S, Kumar A, Anderson B. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One. 2009;4(7):e6229.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zhao J-J, Yang J, Lin J, Yao N, Zhu Y, Zheng J, et al. Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA microarray analysis. Childs Nerv Syst. 2009;25(1):13–20.

    Article  PubMed  Google Scholar 

  23. Marabita F, de Candia P, Torri A, Tegner J, Abrignani S, Rossi RL. Normalization of circulating microRNA expression data obtained by quantitative real-time RT-PCR. Brief Bioinformatics. 2015;17(2):204–12.

    Article  PubMed  Google Scholar 

  24. Wong W, Farr R, Joglekar M, Januszewski A, Hardikar A. Probe-based real-time PCR approaches for quantitative measurement of microRNAs. J Vis Exp. 2015;98:e52586-1-12. https://doi.org/10.3791/52586.

  25. Babapoor S, Horwich M, Wu R, Levinson S, Gandhi M, Makkar H, et al. microRNA in situ hybridization for miR-211 detection as an ancillary test in melanoma diagnosis. Mod Pathol. 2016;29(5):461.

    Article  CAS  PubMed  Google Scholar 

  26. Di Meo A, Saleeb R, Wala SJ, Khella HW, Ding Q, Zhai H, et al. A miRNA-based classification of renal cell carcinoma subtypes by PCR and in situ hybridization. Oncotarget. 2018;9(2):2092.

    Article  PubMed  Google Scholar 

  27. Schwarzkopf M, Pierce NA. Multiplexed miRNA northern blots via hybridization chain reaction. Nucleic Acids Res. 2016;44(15):e129-e.

    Google Scholar 

  28. Rafiee-Pour H-A, Behpour M, Keshavarz M. A novel label-free electrochemical miRNA biosensor using methylene blue as redox indicator: application to breast cancer biomarker miRNA-21. Biosens Bioelectron. 2016;77:202–7.

    Article  CAS  Google Scholar 

  29. Hu T, Zhang L, Wen W, Zhang X, Wang S. Enzyme catalytic amplification of miRNA-155 detection with graphene quantum dot-based electrochemical biosensor. Biosens Bioelectron. 2016;77:451–6.

    Article  CAS  PubMed  Google Scholar 

  30. Goryacheva O, Mishra P, Goryacheva IY. Luminescent quantum dots for miRNA detection. Talanta. 2018;179:456–65.

    Article  CAS  PubMed  Google Scholar 

  31. Zhang J, Yu S-H. Highly photoluminescent silicon nanocrystals for rapid, label-free and recyclable detection of mercuric ions. Nanoscale. 2014;6(8):4096–101.

    Article  CAS  PubMed  Google Scholar 

  32. Sugimoto H, Fujii M, Fukuda Y, Imakita K, Akamatsu K. All-inorganic water-dispersible silicon quantum dots: highly efficient near-infrared luminescence in a wide pH range. Nanoscale. 2014;6(1):122–6.

    Article  CAS  PubMed  Google Scholar 

  33. Inoue A, Sugimoto H, Yaku H, Fujii M. DNA assembly of silicon quantum dots/gold nanoparticle nanocomposites. RSC Adv. 2016;6(68):63933–9.

    Article  CAS  Google Scholar 

  34. Cheng X, McVey BF, Robinson AB, Longatte G, O’Mara PB, Tan VT, et al., editors. Colloidal silicon quantum dots: from preparation to the modification of self-assembled monolayers for bioimaging and sensing applications. Colloidal Nanoparticles for Biomedical Applications XII; 2017: International Society for Optics and Photonics.

  35. Wolfbeis OS. An overview of nanoparticles commonly used in fluorescent bioimaging. Chem Soc Rev. 2015;44(14):4743–68.

    Article  CAS  PubMed  Google Scholar 

  36. Dasog M, Kehrle J, Rieger B, Veinot JG. Silicon nanocrystals and silicon-polymer hybrids: synthesis, surface engineering, and applications. Angew Chem Int Ed. 2016;55(7):2322–39.

    Article  CAS  Google Scholar 

  37. Hassan M, Gomes VG, Dehghani A, Ardekani SM. Engineering carbon quantum dots for photomediated theranostics. Nano Res. 2018;11(1):1–41.

    Article  Google Scholar 

  38. Sun X, Liu Z, Welsher K, Robinson JT, Goodwin A, Zaric S, et al. Nano-graphene oxide for cellular imaging and drug delivery. Nano Res. 2008;1(3):203–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Park K-W, Jung JH. Spectroscopic and electrochemical characteristics of a carboxylated graphene–ZnO composites. J Power Sources. 2012;199:379–85.

    Article  CAS  Google Scholar 

  40. Wu J, Dai J, Shao Y, Sun Y. One-step synthesis of fluorescent silicon quantum dots (Si-QDs) and their application for cell imaging. RSC Adv. 2015;5(102):83581–7.

    Article  CAS  Google Scholar 

  41. Baldwin RK, Pettigrew KA, Ratai E, Augustine MP, Kauzlarich SM. Solution reduction synthesis of surface stabilized silicon nanoparticles. ChemComm. 2002;17:1822–3.

    Google Scholar 

  42. Warner JH, Hoshino A, Yamamoto K, Tilley RD. Water-soluble photoluminescent silicon quantum dots. Angew Chem Int Ed. 2005;44(29):4550–4.

    Article  CAS  Google Scholar 

  43. Hu G, Sun Y, Xie Y, Wu S, Zhang X, Zhuang J, et al. Synthesis of silicon quantum dots with highly efficient full-band UV absorption and their applications in antiyellowing and resistance of photodegradation. ACS Appl Mater Interfaces. 2019;11(6):6634–43.

    Article  CAS  PubMed  Google Scholar 

  44. Dohnalová K, Poddubny AN, Prokofiev AA, De Boer WD, Umesh CP, Paulusse JM, et al. Surface brightens up Si quantum dots: direct bandgap-like size-tunable emission. Light Sci Appl. 2013;2(1):e47-e.

    Article  Google Scholar 

  45. Öğüt S, Chelikowsky JR, Louie SG. Quantum confinement and optical gaps in Si nanocrystals. Phys Rev Lett. 1997;79(9):1770.

    Article  Google Scholar 

  46. Mahani M, Mousapour Z, Divsar F, Nomani A, Ju H. A carbon dot and molecular beacon based fluorometric sensor for the cancer marker microRNA-21. Microchim Acta. 2019;186(3):132.

    Article  Google Scholar 

  47. Pedram P, Mahani M, Torkzadeh-Mahani M, Hasani Z, Ju H. Cadmium sulfide quantum dots modified with the human transferrin protein siderophiline for targeted imaging of breast cancer cells. Microchim Acta. 2016;183(1):67–71.

    Article  CAS  Google Scholar 

  48. Rahimi M, Mahani M, Hassani Z. Carbon quantum dots fluorescence quenching for potassium optode construction. Luminescence. 2019;34(4):402–6.

    Article  CAS  PubMed  Google Scholar 

  49. Wang J, Li R, Long X, Li Z. Synthesis of imidazole-functionalized silicon quantum dots as “off-on” fluorescence probe for highly selective and sensitive detection of l-histidine. Sens Actuators B Chem. 2016;237:740–8.

    Article  CAS  Google Scholar 

  50. Caracciolo G, Palchetti S, Digiacomo L, Zenezini Chiozzi R, Capriotti AL, Amenitsch H, et al. The human biomolecular corona of liposomal doxorubicin: the overlooked factor in anticancer drug delivery. ACS Appl Mater Interfaces. 2018;10(27):22951–62.

    Article  CAS  PubMed  Google Scholar 

  51. Wang C, Xu Z, Zhang C. Polyethyleneimine-functionalized fluorescent carbon dots: water stability, pH sensing, and cellular imaging. ChemNanoMat. 2015;1(2):122–7.

    Article  CAS  Google Scholar 

  52. Yang X, Yang X, Li Z, Li S, Han Y, Chen Y, et al. Photoluminescent carbon dots synthesized by microwave treatment for selective image of cancer cells. J Colloid Interface Sci. 2015;456:1–6.

    Article  CAS  PubMed  Google Scholar 

  53. Yu X, Hu L, Zhang F, Wang M, Xia Z, Wei W. MoS 2 quantum dots modified with a labeled molecular beacon as a ratiometric fluorescent gene probe for FRET-based detection and imaging of microRNA. Microchim Acta. 2018;185(4):239.

    Article  Google Scholar 

  54. Qiu X, Xu J, Guo J, Yahia-Ammar A, Kapetanakis N-I, Duroux-Richard I, et al. Advanced microRNA-based cancer diagnostics using amplified time-gated FRET. Chem Sci. 2018;9(42):8046–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Xi Q, Zhou D-M, Kan Y-Y, Ge J, Wu Z-K, Yu R-Q, et al. Highly sensitive and selective strategy for microRNA detection based on WS2 nanosheet mediated fluorescence quenching and duplex-specific nuclease signal amplification. Anal Chem. 2014;86(3):1361–5.

    Article  CAS  PubMed  Google Scholar 

  56. Larkey NE, Zhang L, Lansing SS, Tran V, Seewaldt VL, Burrows SM. Förster resonance energy transfer to impart signal-on and-off capabilities in a single microRNA biosensor. Analyst. 2016;141(22):6239–50.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the Iran National Science Foundation-Science Deputy of Presidency (Grant No. 94019386) for financial support.

Funding

Mohamad Mahani received Grant No. 94019386 from the Iran National Science Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohamad Mahani.

Ethics declarations

Informed consent

Informed consent was obtained from all individual participants included in the study. The studies were approved by the Research Ethics Committees of Shahid Bahonar University of Kerman (Approval ID: IR.UK.REC.1400.027) and were performed in accordance with the ethical standards.

Conflict of interest

The authors declare that they have 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 4005 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahani, M., Khakbaz, F. & Ju, H. Hairpin oligosensor using SiQDs: Förster resonance energy transfer study and application for miRNA-21 detection. Anal Bioanal Chem 414, 2505–2512 (2022). https://doi.org/10.1007/s00216-022-03891-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-022-03891-1

Keywords

Profiles

  1. Mohamad Mahani