Fluorescent C-NanoDots for rapid detection of BRCA1, CFTR and MRP3 gene mutations

Abstract

The authors report on a fluorometric method for the rapid detection of BRCA1, CFRT and MRP3 gene mutations. These are associated with breast cancer, cystic fibrosis and autoimmune hepatitis diseases, respectively. Carbon nanodots with blue fluorescence (with excitation/emission maxima at 340/440 nm) were synthesized and characterized, and their interactions with DNA were investigated. Changes in the fluorescence intensity following interaction with ssDNA and dsDNA were used for specific DNA sequence of BRCA1, CFRT and MRP3 genes detection. The response to DNAs is linear up to 200 nM and the detection limit is 270 pM. The assay selectivity allows the detection of single gene mutations. Under optimum conditions, the assay can rapidly discriminate between wild type and mutated samples.

Schematic representation of fluorescence assay for rapid detection of gene mutation based on fluorescent carbon nanodots.

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References

  1. 1.

    Cattrall RW (1997) Chemical sensors, chemistry primers. Oxford University Press, Oxford

    Google Scholar 

  2. 2.

    Mickelsen SR (1996) Electrochemical biosensors for DNA sequence detection. Electroanalysis 8:15–19

    Article  Google Scholar 

  3. 3.

    Palecek E, Fojta M, Tomschik M, Wang J (1998) Electrochemical biosensors for DNA hybridization and DNA damage. Biosens Bioelectron 13:621–628

    CAS  Article  Google Scholar 

  4. 4.

    Wang J (2006) Electrochemical biosensors: towards point-of-care cancer diagnostics. Biosens Bioelectron 21:1887–1892

    CAS  Article  Google Scholar 

  5. 5.

    Miao P, Liu L, Nie YJ, Li GX (2009) An electrochemical sensing strategy for ultrasensitive detection of glutathione by using two gold electrodes and two complementary oligonucleotides. Biosens Bioelectron 24:3347–3351

    CAS  Article  Google Scholar 

  6. 6.

    Wan Y, Zhang J, Liu G, Pan D, Wang LH, Song SP, Fan CH (2009) Ligase-based multiple DNA analysis by using an electrochemical sensor array. Biosens Bioelectron 24:1209–1212

    CAS  Article  Google Scholar 

  7. 7.

    Ma H, Li Z, Xue N, Cheng Z, Miao X (2018) A gold nanoparticle based fluorescent probe for simultaneous recognition of single-stranded DNA and double-stranded DNA. Microchim Acta 185:93

    Article  Google Scholar 

  8. 8.

    Qian ZS, Shan XY, Chai LJ, Ma JJ, Chen JR, Feng H (2014) A universal fluorescence sensing strategy based on biocompatible graphene quantum dots and graphene oxide for the detection of DNA. Nanoscale 6:5671–5674

    CAS  Article  Google Scholar 

  9. 9.

    Li HT, Kang ZH, Liu Y, Lee ST (2012) Carbon nanodots: synthesis, properties and applications. J Mater Chem 22:24230–24253

    CAS  Article  Google Scholar 

  10. 10.

    Zhong D, Zhuo Y, Feng YJ, Yang XM (2015) Employing carbon dots modified with vancomycin for assaying Gram-positive bacteria like Staphylococcus aureus. Biosens Bioelectron 74:546–553

    CAS  Article  Google Scholar 

  11. 11.

    García-Mendiola T, Bravo I, López-Moreno JM, Pariente F, Wannemacher R, Weber K, Popp J, Lorenzo E (2018) Carbon nanodots based biosensors for gene mutation detection. Sens Actuators B: Chem 256:226–233

    Article  Google Scholar 

  12. 12.

    D'Andrea E, Marzuillo C, De Vito C, Di Marco M, Pitini E, Vacchio MR, Villari P (2016) Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations. Genet Med 18:1171–1180

    Article  Google Scholar 

  13. 13.

    Marmur J (1961) Procedure for isolation of deoxyribonucleic acid from micro-organisms. J Mol Biol 3:208–218

    CAS  Article  Google Scholar 

  14. 14.

    Doty P, Rice SA (1955) The denaturation of Desoxypentose nucleic acid. Biochim Biophys Acta 16:446–448

    CAS  Article  Google Scholar 

  15. 15.

    Horcas I, Fernández R, Gómez-Rodríguez JM, Colchero J, Gómez-Herrero J, Baro AM (2007) WSXM: a software for scanning probe microscopy and a tool for nanotechnology. Rev Sci Instrum 78:013705

    CAS  Article  Google Scholar 

  16. 16.

    Baker SN, Baker GA (2010) Luminescent carbon Nanodots: emergent Nanolights. Angew Chem Int Ed 49:6726–6744

    CAS  Article  Google Scholar 

  17. 17.

    Shen JH, Zhu YH, Yang XL, Li CZ (2012) Graphene quantum dots: emergent nanolights for bioimaging, sensors, catalysis and photovoltaic devices. Chem Commun 48:3686–3699

    CAS  Article  Google Scholar 

  18. 18.

    Zhang ZP, Zhang J, Chen N, Qu LT (2012) Graphene quantum dots: an emerging material for energy-related applications and beyond. Energy Environ Sci 5:8869–8890

    CAS  Article  Google Scholar 

  19. 19.

    Zhu SJ, Tang SJ, Zhang JH, Yang B (2012) Control the size and surface chemistry of graphene for the rising fluorescent materials. Chem Commun 48:4527–4539

    CAS  Article  Google Scholar 

  20. 20.

    Cao L, Meziani MJ, Sahu S, Sun YP (2013) Photoluminescence properties of graphene versus other carbon nanomaterials. Acc Chem Res 46:171–180

    CAS  Article  Google Scholar 

  21. 21.

    Li LL, Wu GH, Yang GH, Peng J, Zhao JW, Zhu JJ (2013) Focusing on luminescent graphene quantum dots: current status and future perspectives. Nanoscale 5:4015–4039

    CAS  Article  Google Scholar 

  22. 22.

    Li LL, Ji J, Fei R, Wang CZ, Lu Q, Zhang JR, Jiang LP, Zhu JJ (2012) A facile microwave avenue to electrochemiluminescent two-color graphene quantum dots. Adv Funct Mater 22:2971–2979

    CAS  Article  Google Scholar 

  23. 23.

    Wang YF, Hu AG (2014) Carbon quantum dots: synthesis, properties and applications. J Mater Chem C 2:6921–6939

    CAS  Article  Google Scholar 

  24. 24.

    Chen L, Han HY (2014) Recent advances in the use of near-infrared quantum dots as optical probes for bioanalytical, imaging and solar cell application. Microchim Acta 181:1485–1495

    CAS  Article  Google Scholar 

  25. 25.

    Borghei Y, Hosseini M, Ganjali MR (2017) Detection of large deletion in human BRCA1 gene in human breast carcinoma MCF-7 cells by using DNA-silver nanoclusters. Methods Appl Fluoresc 6:015001

    Article  Google Scholar 

  26. 26.

    He H, Chan DS, Leung C, Ma D (2012) A highly selective G-quadruplex-based luminescent switch-on probe for the detection of gene deletion. Chem Commun 48:9462–9464

    CAS  Article  Google Scholar 

  27. 27.

    Zhu SJ, Meng QN, Wang L, Zhang JH, Song YB, Jin H, Zhang K, Sun HC, Wang HY, Yang B (2013) Highly Photoluminescent carbon dots for multicolor patterning, sensors, and bioimaging. Angew Chem Int Ed 52:3953–3957

    CAS  Article  Google Scholar 

  28. 28.

    Wen Z, Yin X (2016) Excitation-independent carbon dots, from photoluminescence mechanism to single-color application. RSC Adv 6:27829–27835

    CAS  Article  Google Scholar 

  29. 29.

    Mergny JL, Duval-Valentin G, Nguyen CH, Perrouault L, Faucon B, Rougée M, Montenay-Garestier T, Bisagni E, Hélène C (1992) Triple Helix-specific ligands. Science 256:1681–1684

    CAS  Article  Google Scholar 

  30. 30.

    Kumar CV, Turner RS, Asuncion EH (1993) Groove binding of a styrylcyanine dye to the DNA double helix: the salt effect. J Photochem Photobiol A Chem 74:231–238

    CAS  Article  Google Scholar 

  31. 31.

    Cosa G, Focsaneanu KS, McLean JRN, McNamee JP, Scaiano JC (2001) Photophysical properties of fluorescent DNA-dyes bound to single- and double-stranded DNA in aqueous buffered solution. Photochem Photobiol 73:585–599

    CAS  Article  Google Scholar 

  32. 32.

    Heli H, Moosavi-Movahedi AA, Jabbari A, Ahmad F (2007) An electrochemical study of safranin O binding to DNA at the surface. J Solid State Electrochem 11:593–599

    CAS  Article  Google Scholar 

  33. 33.

    Lakowicz JR (2006) Principles of fluorescence spectroscopy. Springer Science+Business Media, New York

    Book  Google Scholar 

Download references

Acknowledgements

CAM projects: TRANSNANOAVANSENS-CM (S2018/NMT-4349) and MAD2D-CM Program. MEIC projects: CTQ2017-84309-C2-1-R and MAT2015-71879-P. We thank the Confocal Microscopy and Flow Cytometry Services of CBMSO.

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Correspondence to Encarnación Lorenzo.

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García-Mendiola, T., Elosegui, C.G., Bravo, I. et al. Fluorescent C-NanoDots for rapid detection of BRCA1, CFTR and MRP3 gene mutations. Microchim Acta 186, 293 (2019). https://doi.org/10.1007/s00604-019-3386-9

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Keywords

  • Rapid assay
  • Cancer
  • Fluorescent carbon nanodots
  • DNA sensing
  • Mutations
  • Genetic diseases
  • Fluorescent assay