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DNAzyme-functionalized porous carbon nanospheres serve as a fluorescent nanoprobe for imaging detection of microRNA-21 and zinc ion in living cells

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Abstract

The present study shows that a dual-signal nanoprobe consisting of DNAzyme-functionalized porous carbon nanospheres (PCNs) responds to microRNA-21 and zinc ion (Zn2+). The fluorescent probe undergoes an increase in the fluorescence intensity of fluorescein isothiocyanate (FITC) (with excitation/emission wavelengths at 488/517 nm) and the fluorescence intensity of cyanine-5 (Cy5) (with excitation/emission wavelengths at 633/670 nm) in the presence of microRNA-21 and Zn2+. The recognition between microRNA-21 and its complementary strand in the PCNs induces the separation of Zn2+-specific DNAzyme from PCNs, thus resulting in the increase of green fluorescence, and the exogenous Zn2+ triggers the rupture of cleavage strand of DNAzyme and recovery of red fluorescence. This nanoprobe allows us to acquire in vitro the determination of microRNA-21 in the range of 2–300 nM with a detection limit of 0.57 nM and the determination of Zn2+ in the range 2–100 nM with a detection limit of 0.43 nM, and in situ simultaneous imaging in MCF-7 breast cancer cells. Therefore, this strategy permits to obtain the expression levels of different biomarkers in living cells, providing a useful tool for diagnosis of cancers and understanding their biological process.

Schematic representation of the DNAzyme-functionalized porous carbon nanospheres for the imaging analysis of microRNA-21 and Zn2+ in living cells.

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References

  1. Montalti M, Cantelli A, Battistelli G (2015) Nanodiamonds and silicon quantum dots: ultrastable and biocompatible luminescent nanoprobes for long-term bioimaging. Chem Soc Rev 44(14):4853–4921. https://doi.org/10.1039/c4cs00486h

    Article  CAS  PubMed  Google Scholar 

  2. Wolfbeis OS (2015) An overview of nanoparticles commonly used in fluorescent bioimaging. Chem Soc Rev 44(14):4743–4768. https://doi.org/10.1039/c4cs00392f

    Article  CAS  PubMed  Google Scholar 

  3. Chen L-Y, Wang C-W, Yuan Z, Chang H-T (2014) Fluorescent gold nanoclusters: recent advances in sensing and imaging. Anal Chem 87(1):216–229. https://doi.org/10.1021/ac503636j

    Article  CAS  PubMed  Google Scholar 

  4. Ng VWK, Berti R, Lesage F, Kakkar A (2013) Gold: a versatile tool for in vivo imaging. J Mater Chem B 1(1):9–25. https://doi.org/10.1039/c2tb00020b

    Article  CAS  PubMed  Google Scholar 

  5. Baeissa A, Dave N, Smith BD, Liu J (2010) DNA-functionalized monolithic hydrogels and gold nanoparticles for colorimetric DNA detection. ACS Appl Mater Interfaces 2(12):3594–3600. https://doi.org/10.1021/am100780d

    Article  CAS  PubMed  Google Scholar 

  6. Moros M, Kyriazi ME, El-Sagheer AH, Brown T, Tortiglione C, Kanaras AG (2019) DNA-coated gold nanoparticles for the detection of mRNA in live Hydra vulgaris animals. ACS Appl Mater Interfaces 11(15):13905–13911. https://doi.org/10.1021/acsami.8b17846

    Article  CAS  PubMed  Google Scholar 

  7. Yasun E, Gulbakan B, Ocsoy I, Yuan Q, Shukoor MI, Li C, Tan W (2012) Enrichment and detection of rare proteins with aptamer-conjugated gold nanorods. Anal Chem 84(14):6008–6015. https://doi.org/10.1021/ac300806s

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kim SU, Jo EJ, Noh Y, Mun H, Ahn YD, Kim MG (2018) Adenosine triphosphate bioluminescence-based bacteria detection using targeted photothermal lysis by gold nanorods. Anal Chem 90(17):10171–10178. https://doi.org/10.1021/acs.analchem.8b00254

    Article  CAS  PubMed  Google Scholar 

  9. Xu S, Jiang L, Nie Y, Wang J, Li H, Liu Y, Wang W, Xu G, Luo X (2018) Gold nanobipyramids as dual-functional substrates for in situ “turn on” analyzing intracellular telomerase activity based on target-triggered plasmon-enhanced fluorescence. ACS Appl Mater Interfaces 10(32):26851–26858. https://doi.org/10.1021/acsami.8b05447

    Article  CAS  PubMed  Google Scholar 

  10. Martynenko IV, Litvin AP, Purcell-Milton F, Baranov AV, Fedorov AV, Gun’ko YK (2017) Application of semiconductor quantum dots in bioimaging and biosensing. J Mater Chem B 5(33):6701–6727. https://doi.org/10.1039/c7tb01425b

    Article  CAS  PubMed  Google Scholar 

  11. Kehr NS (2016) Enantiomorphous periodic mesoporous organosilica-based nanocomposite hydrogel scaffolds for cell adhesion and cell enrichment. Biomacromolecules 17(3):1117–1122. https://doi.org/10.1021/acs.biomac.5b01739

    Article  CAS  PubMed  Google Scholar 

  12. Kharkar PM, Kiick KL, Kloxin AM (2013) Designing degradable hydrogels for orthogonal control of cell microenvironments. Chem Soc Rev 42(17):7335–7372. https://doi.org/10.1039/c3cs60040h

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Xue B, Kozlovskaya V, Kharlampieva E (2017) Shaped stimuli-responsive hydrogel particles: syntheses, properties and biological responses. J Mater Chem B 5(1):9–35. https://doi.org/10.1039/c6tb02746f

    Article  CAS  PubMed  Google Scholar 

  14. Lei K, Ma Q, Yu L, Ding J (2016) Functional biomedical hydrogels for in vivo imaging. J Mater Chem B 4(48):7793–7812. https://doi.org/10.1039/c6tb02019d

    Article  CAS  PubMed  Google Scholar 

  15. Lei Z, Christov N, Zhang LL, Zhao XS (2011) Mesoporous carbon nanospheres with an excellent electrocapacitive performance. J Mater Chem B 21(7):2274–2281. https://doi.org/10.1039/c0jm03322g

    Article  CAS  Google Scholar 

  16. Wang T, Zhang P, Sun Y, Liu B, Liu Y, Qiao Z-A, Huo Q, Dai S (2017) New polymer colloidal and carbon nanospheres: stabilizing ultrasmall metal nanoparticles for solvent-free catalysis. Chem Mater 29(9):4044–4051. https://doi.org/10.1021/acs.chemmater.7b00710

    Article  CAS  Google Scholar 

  17. Li S, Pasc A, Fierro V, Celzard A (2016) Hollow carbon spheres, synthesis and applications – a review. J Mater Chem A 4(33):12686–12713. https://doi.org/10.1039/c6ta03802f

    Article  CAS  Google Scholar 

  18. Zhang P, Qiao ZA, Dai S (2015) Recent advances in carbon nanospheres: synthetic routes and applications. Chem Commun 51(45):9246–9256. https://doi.org/10.1039/c5cc01759a

    Article  CAS  Google Scholar 

  19. Barnham KJ, Bush AI (2008) Metals in Alzheimer’s and Parkinson’s diseases. Curr Opin Chem Biol 12(2):222–228. https://doi.org/10.1016/j.cbpa.2008.02.019

    Article  CAS  PubMed  Google Scholar 

  20. McAllum EJ, Finkelstein DI (2016) Metals in Alzheimer’s and Parkinson’s disease: relevance to dementia with Lewy bodies. J Mol Neurosci 60(3):279–288. https://doi.org/10.1007/s12031-016-0809-5

    Article  CAS  PubMed  Google Scholar 

  21. Wu L, Guo QS, Liu YQ, Sun QJ (2015) Fluorescence resonance energy transfer-based ratiometric fluorescent probe for detection of Zn(2+) using a dual-emission silica-coated quantum dots mixture. Anal Chem 87(10):5318–5323. https://doi.org/10.1021/acs.analchem.5b00514

    Article  CAS  PubMed  Google Scholar 

  22. Xu H, Miao R, Fang Z, Zhong X (2011) Quantum dot-based “turn-on” fluorescent probe for detection of zinc and cadmium ions in aqueous media. Anal Chim Acta 687(1):82–88. https://doi.org/10.1016/j.aca.2010.12.002

    Article  CAS  PubMed  Google Scholar 

  23. Wu Q, Zhou M, Shi J, Li Q, Yang M, Zhang Z (2017) Synthesis of water-soluble Ag2S quantum dots with fluorescence in the second near-infrared window for turn-on detection of Zn (II) and cd (II). Anal Chem 89(12):6616–6623. https://doi.org/10.1021/acs.analchem.7b00777

    Article  CAS  PubMed  Google Scholar 

  24. Luo X, Wu W, Deng F, Chen D, Luo S, Au C (2014) Quantum dot-based turn-on fluorescent probe for imaging intracellular zinc (II) and cadmium (II) ions. Microchim Acta 181(11–12):1361–1367. https://doi.org/10.1007/s00604-014-1264-z

    Article  CAS  Google Scholar 

  25. He D, He X, Yang X, Li HW (2017) A smart ZnO@polydopamine-nucleic acid nanosystem for ultrasensitive live cell mRNA imaging by the target-triggered intracellular self-assembly of active DNAzyme nanostructures. Chem Sci 8(4):2832–2840. https://doi.org/10.1039/c6sc04633a

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yang Z, Loh KY, Chu Y-T, Feng R, Satyavolu NSR, Xiong M, Nakamata Huynh SM, Hwang K, Li L, Xing H, Zhang X, Chemla YR, Gruebele M, Lu Y (2018) Optical control of metal ion probes in cells and Zebrafish using highly selective DNAzymes conjugated to upconversion nanoparticles. J Am Chem Soc 140(50):17656–17665. https://doi.org/10.1021/jacs.8b09867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang W, Satyavolu NSR, Wu Z, Zhang JR, Zhu JJ, Lu Y (2017) Near-infrared photothermally activated DNAzyme-gold nanoshells for imaging metal ions in living cells. Angew Chem Int Ed Eng 56(24):6798–6802. https://doi.org/10.1002/anie.201701325

    Article  CAS  Google Scholar 

  28. Yang C, Yin X, Huan SY, Chen L, Hu XX, Xiong MY, Chen K, Zhang XB (2018) Two-photon DNAzyme-gold nanoparticle probe for imaging intracellular metal ions. Anal Chem 90(5):3118–3123. https://doi.org/10.1021/acs.analchem.7b04171

    Article  CAS  PubMed  Google Scholar 

  29. Ryan BM, Robles AI, Harris CC (2010) Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 10(6):389–402. https://doi.org/10.1038/nrc2867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tricoli JV, Jacobson JW (2007) MicroRNA: potential for cancer detection, diagnosis, and prognosis. Cancer Res 67(10):4553–4555. https://doi.org/10.1158/0008-5472.CAN-07-0563

    Article  CAS  PubMed  Google Scholar 

  31. Luo J, Xu Y, Huang J, Zhang S, Xu Q, He J (2017) Enzyme-free amplified detection of circulating microRNA by making use of DNA circuits, a DNAzyme, and a catalytic hairpin assembly. Microchim Acta 185(1):38. https://doi.org/10.1007/s00604-017-2565-9

    Article  CAS  Google Scholar 

  32. Mahani M, Mousapour Z, Divsar F, Nomani A, Ju H (2019) A carbon dot and molecular beacon based fluorometric sensor for the cancer marker microRNA-21. Microchim Acta 186(3):132. https://doi.org/10.1007/s00604-019-3233-z

    Article  CAS  Google Scholar 

  33. Yang L, Ren Y, Pan W, Yu Z, Tong L, Li N, Tang B (2016) Fluorescent nanocomposite for visualizing cross-talk between MicroRNA-21 and hydrogen peroxide in ischemia-reperfusion injury in live cells and in vivo. Anal Chem 88(23):11886–11891. https://doi.org/10.1021/acs.analchem.6b03701

    Article  CAS  PubMed  Google Scholar 

  34. Yi JT, Chen TT, Huo J, Chu X (2017) Nanoscale zeolitic imidazolate framework-8 for ratiometric fluorescence imaging of MicroRNA in living cells. Anal Chem 89(22):12351–12359. https://doi.org/10.1021/acs.analchem.7b03369

    Article  CAS  PubMed  Google Scholar 

  35. Wang G, Fu Y, Ren Z, Huang J, Best S, Li X, Han G (2018) Upconversion nanocrystal ‘armoured’ silica fibres with superior photoluminescence for microRNA detection. Chem Commun 54(49):6324–6327. https://doi.org/10.1039/c8cc03480j

    Article  CAS  Google Scholar 

  36. Xia X, Hao Y, Hu S, Wang J (2014) Hairpin DNA probe with 5′-TCC/CCC-3′ overhangs for the creation of silver nanoclusters and microRNA assay. Biosens Bioelectron 51:36–39. https://doi.org/10.1016/j.bios.2013.07.036

    Article  CAS  PubMed  Google Scholar 

  37. Yang Y, Huang J, Yang X, He X, Quan K, Xie N, Ou M, Wang K (2017) Gold nanoparticle based hairpin-locked-DNAzyme probe for amplified microRNA imaging in living cells. Anal Chem 89(11):5850–5856. https://doi.org/10.1021/acs.analchem.7b00174

    Article  CAS  PubMed  Google Scholar 

  38. Wu Y, Huang J, Yang X, Yang Y, Quan K, Xie N, Li J, Ma C, Wang K (2017) Gold nanoparticle loaded split-DNAzyme probe for amplified microRNA detection in living cells. Anal Chem 89(16):8377–8383. https://doi.org/10.1021/acs.analchem.7b01632

    Article  CAS  PubMed  Google Scholar 

  39. Bin DS, Chi ZX, Li Y, Zhang K, Yang X, Sun YG, Piao JY, Cao AM, Wan LJ (2017) Controlling the compositional chemistry in single nanoparticles for functional hollow carbon nanospheres. J Am Chem Soc 139(38):13492–13498. https://doi.org/10.1021/jacs.7b07027

    Article  CAS  PubMed  Google Scholar 

  40. Wang H, Li X, Ma Z, Wang D, Wang L, Zhan J, She L, Yang F (2016) Hydrophilic mesoporous carbon nanospheres with high drug-loading efficiency for doxorubicin delivery and cancer therapy. Int J Nanomedicine 11:1793–1806. https://doi.org/10.2147/IJN.S103020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Li D, Teoh WY, Gooding JJ, Selomulya C, Amal R (2010) Functionalization strategies for protease immobilization on magnetic nanoparticles. Adv Funct Mater 20(11):1767–1777. https://doi.org/10.1002/adfm.201000188

    Article  CAS  Google Scholar 

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Acknowledgments

The authors greatly acknowledge support from the Project Fund for Shangdong Key R&D Program (2017GGX20121). In addition, Xiaoting Ji particularly wishes to thank Zhan Xiao, whose sincere personality has given her powerful spiritual impetus to overcome various difficulties in her doctoral research.

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Correspondence to Shuyan Niu or Caifeng Ding.

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Ji, X., Wang, Z., Niu, S. et al. DNAzyme-functionalized porous carbon nanospheres serve as a fluorescent nanoprobe for imaging detection of microRNA-21 and zinc ion in living cells. Microchim Acta 187, 249 (2020). https://doi.org/10.1007/s00604-020-04226-6

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