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A novel binding-induced DNAzyme motor triggered by survivin mRNA

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Abstract

The accurate and sensitive detection of survivin mRNA is of great significance for cancer diagnosis and treatment. However, limited by the low-abundance mRNA in live cells, most strategies of survivin mRNA detection that were one-to-one signal-triggered model (one target triggered one signal) were inapplicable in practice. Here, we reported a binding-induced DNAzyme motor triggered by the survivin mRNA, which was a one-to-more signal-triggered model (one target triggered more signals), amplifying the detection signal and enhancing the sensitivity. The nanomotor is constructed by assembling several DNAzyme motor strands silenced by the blocker strands, and dozens of FAM-labeled substrate strands on a single gold nanoparticle (AuNP), forming three-dimensional DNA tracks. Through building the survivin mRNA bridge between the blocker and the DNAzyme motor strand, the binding-induced DNA nanomotor could be triggered by survivin mRNA. The operation of the DNAzyme motor was self-powered. And each walking step of the DNAzyme motor was fueled by DNAzyme-catalyzed substrate cleavage, along with the cleavage of the fluorescent molecule, resulting in autonomous and progressive walking along the AuNP-based tracks, and the fluorescence increase. The DNAzyme motor exhibited excellent sensitivity and remarkable specificity for survivin mRNA, providing the potential for cell image.

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References

  1. Liu M, Fu J, Hejesen C, Yang Y, Woodbury NW, Gothelf K, Liu Y. A DNA tweezer-actuated enzyme nanoreactor. Nat Commun. 2013;4:2127.

    Article  PubMed  CAS  Google Scholar 

  2. Yurke B, Turberfield AJ, Mills AP, Simmel FC, Neumann JL. A DNA-fuelled molecular machine made of DNA. Nature. 2000;406:605–8.

    Article  CAS  PubMed  Google Scholar 

  3. Cha TG, Pan J, Chen H, Salgado J, Li X, Mao C, Choi JH. A synthetic DNA motor that transports nanoparticles along carbon nanotubes. Nat Nanotech. 2014;9:39–43.

    Article  CAS  Google Scholar 

  4. Yin P, Yan H, Daniell XG, Turberfield AJ, Reif JH. A unidirectional DNA walker that moves autonomously along a track. Angew Chem. 2004;116:5014–9.

    Article  Google Scholar 

  5. Thomas JM, Yu HZ, Sen D. A mechano-electronic DNA switch. J Am Chem Soc. 2012;134:13738–48.

    Article  CAS  PubMed  Google Scholar 

  6. Wang F, Liu X, Willner I. DNA switches: from principles to applications. Angew Chem Int Ed. 2015;54:1098–129.

    Article  CAS  Google Scholar 

  7. Bujold KE, Lacroix A, Sleiman HF. DNA nanostructures at the interface with biology. Chem. 2018;4:495–521.

    Article  CAS  Google Scholar 

  8. Zhao J, Chu H, Zhao Y, Lu Y, Li L. A NIR light gated DNA nanodevice for spatiotemporally controlled imaging of microRNA in cells and animals. J Am Chem Soc. 2019;141:7056–62.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang S, Chen C, Xue C, Chang D, Xu H, Salena BJ, Li Y, Wu ZS. Ribbon of DNA lattice on gold nanoparticles for selective drug delivery to cancer cells. Angew Chem Int Ed. 2020;59:14584–92.

    Article  CAS  Google Scholar 

  10. Qing ZH, Xu JY, Hu JL, Zheng J, He L, Zou Z, Yang S, Tan WH, Yang RH. In situ amplification-based imaging of RNA in living cells. Angew Chem. 2019;131:11698–709.

    Article  Google Scholar 

  11. Fong FY, Oh SS, Hawker CJ, Soh HT. In vitro selection of pH-activated DNA nanostructures. Angew Chem Int Ed. 2016;55:15258–62.

    Article  CAS  Google Scholar 

  12. You M, Chen Y, Zhang X, Liu H, Wang R, Wang K, Williams KR, Tan W. An autonomous and controllable light-driven DNA walking device. Angew Chem Int Ed. 2012;51:2457–60.

    Article  CAS  Google Scholar 

  13. Wang W, Satyavolu NSR, Wu Z, Zhang JR, Zhu JJ, Lu Y. Near-infrared photothermally activated DNAzyme-gold nanoshells for imaging metal ions in living cells. Angew Chem Int Ed. 2017;56:6798–802.

    Article  CAS  Google Scholar 

  14. Peng HY, Newbigging AM, Reid MS, Uppal JS, Xu JY, Zhang HQ, Le XC. Signal amplification in living cells: a review of microRNA detection and imaging. Anal Chem. 2020;92:292–308.

    Article  CAS  PubMed  Google Scholar 

  15. Ratajczak K, Krazinski BE, Kowalczyk AE, Dworakowska B, Jakiela S, Stobiecka M. Hairpin−hairpin molecular beacon interactions for detection of survivin mRNA in malignant SW480 cells. ACS Appl Mater Interfaces. 2018;10:17028–39.

    Article  CAS  PubMed  Google Scholar 

  16. Seferos DS, Giljohann DA, Hill HD, Prigodich AE, Mirkin CA. Nano-flares: probes for transfection and mRNA detection in living cells. J Am Chem Soc. 2007;129:15477–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Khan S, Burciu B, Filipe CDM, Li Y, Dellinger K, Didar TF. DNAzyme-based biosensors: immobilization strategies, applications, and future prospective. ACS Nano. 2021;15:13943–69.

    Article  CAS  PubMed  Google Scholar 

  18. Cheng X, Sun R, Yin L, Chai Z, Shi H, Gao M. Light-triggered assembly of gold nanoparticles for photothermal therapy and photoacoustic imaging of tumors in vivo. Adv Mater. 2017;29:1604894.

    Article  CAS  Google Scholar 

  19. Zheng D, Seferos DS, Giljohann DA, Patel PC, Mirkin CA. Aptamer nano-flares for molecular detection in living cells. Nano Lett. 2009;9:3258–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li N, Chang C, Pan W, Tang B. A multicolor nanoprobe for detection and imaging of tumor-related mRNAs in living cells. Angew Chem Int Ed. 2012;51:7426–30.

    Article  CAS  Google Scholar 

  21. Kyriazi ME, Giust D, El-Sagheer AH, Lackie PM, Muskens OL, Brown T, Kanaras AG. Multiplexed mRNA sensing and combinatorial-targeted drug delivery using DNA-Gold nanoparticle dimers. ACS Nano. 2018;12:3333–40.

    Article  CAS  PubMed  Google Scholar 

  22. Huang J, He Y, Yang X, Wang K, Ying L, Quan K, Yang Y, Yin B. I-motif-based nano-flares for sensing pH changes in live cells. Chem Commun. 2014;50:15768–71.

    Article  CAS  Google Scholar 

  23. Li J, Huang J, Yang X, Yang Y, Quan K, Xie N, Wu Y, Ma C, Wang K. Two-color-based nanoflares for multiplexed microRNAs imaging in live cells. Nanotheranostics. 2018;2:96–105.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zhao XJ, Zhu ZC, Zou R, Wang LY, Gong H, Cai CQ. An enzyme-free three-dimensional DNA walker powered by catalytic hairpin assembly for H5N1 DNA ratiometric detection. Microchem J. 2021;17:106728.

    Article  CAS  Google Scholar 

  25. Du H, Yang P, Hou X, Hou XD, Chen JB. Accelerating DNA nanomotor by branched DNAzyme for ultrasensitive optical detection of thrombin. Microchem J. 2018;139:260–7.

    Article  CAS  Google Scholar 

  26. Liu Z, Zhao J, Zhang R, Han G, Zhang C, Liu B, Zhang Z, Han MY, Gao X. Cross-platform cancer cell identification using telomerase-specific spherical nucleic acids. ACS Nano. 2018;12:3629–37.

    Article  CAS  PubMed  Google Scholar 

  27. He X, Zeng T, Li Z, Wang G, Ma N. Catalytic molecular imaging of microRNA in living cells by DNA-programmed nanoparticle disassembly. Angew Chem Int Ed. 2016;55:3073–6.

    Article  CAS  Google Scholar 

  28. Liang CP, Ma PQ, Liu H, Guo X, Yin BC, Ye BC. Rational engineering of a dynamic, entropy-driven DNA nanomachine for intracellular microRNA imaging. Angew Chem Int Ed. 2017;56:9077–81.

    Article  CAS  Google Scholar 

  29. Wang J, Huang J, Quan K, Li J, Wu Y, Wei Q, Yang X, Wang K. Hairpin-fuelled catalytic nanobeacons for amplified microRNA imaging in live cells. Chem Commun. 2018;54:10336–9.

    Article  CAS  Google Scholar 

  30. Yang Y, Huang J, Yang X, Quan K, Wang H, Ying L, Xie N, Ou M, Wang K. Aptazyme-Gold nanoparticle sensor for amplified molecular probing in living cells. Anal Chem. 2016;88:5981–7.

    Article  CAS  PubMed  Google Scholar 

  31. Liu J, Cui M, Zhou H, Yang W. DNAzyme based nanomachine for in situ detection of microRNA in living cells. ACS Sensors. 2017;2:1847–53.

    Article  CAS  PubMed  Google Scholar 

  32. Yang Y, Huang J, Yang X, He X, Quan K, Xie N, Ou M, Wang K. Gold nanoparticle based hairpin-locked-DNAzyme probe for amplified miRNA imaging in living cells. Anal Chem. 2017;89:5850–6.

    Article  CAS  PubMed  Google Scholar 

  33. Hu N, Wang Y, Liu C, He M, Nie C, Zhang J, Yu Q, Zhao C, Chen T, Chu X. An enzyme-initiated DNAzyme motor for RNase H activity imaging in living cell. Chem Commun. 2020;56:639–42.

    Article  CAS  Google Scholar 

  34. Wu Y, Huang J, Yang X, Yang Y, Quan K, Xie N, Li J, Ma C, Wang K. Gold nanoparticle loaded split-DNAzyme probe for amplified miRNA detection in living cells. Anal Chem. 2017;89:8377–83.

    Article  CAS  PubMed  Google Scholar 

  35. Peng H, Li XF, Zhang H, Le XC. A microRNA-initiated DNAzyme motor operating in living cells. Nat Commun. 2017;8:14378.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Liu C, Hu Y, Pan Q, Yi J, Zhang J, He M, He M, Chen T, Chu X. A microRNA-triggered self-powered DNAzyme walker operating in living cells. Biosens Bioelectron. 2019;136:31–7.

    Article  CAS  PubMed  Google Scholar 

  37. Liu C, Hu Y, Pan Q, Yi J, Zhang J, He M, He M, Nie C, Chen T, Chu X. A photocontrolled and self-powered bipedal DNA walking machine for intracellular microRNA imaging. Chem Commun. 2020;56:3496–9.

    Article  CAS  Google Scholar 

  38. Wu Z, Liu GQ, Yang XL, Jiang JH. Electrostatic nucleic acid nanoassembly enables hybridization chain reaction in living cells for ultrasensitive mRNA imaging. J Am Chem Soc. 2015;137:6829–36.

    Article  CAS  PubMed  Google Scholar 

  39. Wang J, Wang DX, Tang AN, Kong DM. Highly integrated, biostable, and self-powered DNA motor enabling autonomous operation in living bodies. Anal Chem. 2019;91:5244–51.

    Article  CAS  PubMed  Google Scholar 

  40. Liu YH, Gao JL, Liu JX, Liu D, Fang WK, Zheng B, Tang HW, Li CY. Photo-gated and self-powered three-dimensional DNA motors with boosted biostability for exceptionally precise and efficient tracing of intracellular survivin mRNA. Biosens Bioelectron. 2021;190:113445.

    Article  CAS  PubMed  Google Scholar 

  41. Zhang H, Lai M, Zuehlke A, Peng H, Li XF, Le XC. Binding-induced DNA nanomachines triggered by proteins and nucleic acids. Angew Chem. 2015;127:14534–8.

    Article  Google Scholar 

  42. Grabar KC, Freeman RG, Hommer MB, Natan MJ. Preparation and characterization of Au colloid monolayers. Anal Chem. 1995;67:735–43.

    Article  CAS  Google Scholar 

  43. Gao P, Wei R, Chen Y, Liu X, Zhang J, Pan W, Li N, Tang B. Multicolor covalent organic framework-DNA nanoprobe for fluorescence imaging of biomarkers with different locations in living cells. Anal Chem. 2021;93:13734–41.

    Article  CAS  PubMed  Google Scholar 

  44. Piao Y, Liu F, Seo TS. A novel molecular beacon bearing a graphite nanoparticle as a nanoquencher for in situ mRNA detection in cancer cells. ACS Appl Mater Inter. 2012;4:6785–9.

    Article  CAS  Google Scholar 

  45. Ren K, Xu Y, Liu Y, Yang M, Ju H. A responsive “nano string light” for highly efficient mRNA imaging in living cells via accelerated DNA cascade reaction. ACS Nano. 2018;12:263–71.

    Article  CAS  PubMed  Google Scholar 

  46. Qian GS, Kang B, Zhang ZL, Li XL, Zhao W, Xu JJ, Chen HY. Plasmonic nanohalo optical probes for highly sensitive imaging of survivin mRNA in living cells. Chem Commun. 2016;52:11052–5.

    Article  CAS  Google Scholar 

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Funding

Financial support from the Scientific Research Fund of Hunan Provincial Education Department (21C0566, 21A0455), the Natural Science Foundation of Hunan Province (2020JJ2012), the National Natural Science Foundation of China (81874332), and the Natural Science Foundation of Hunan Province, China (2020JJ5593).

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Correspondence to Chang Liu, Guoqiang Zou or Hai Yang.

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Liu, C., Deng, J., Yi, J. et al. A novel binding-induced DNAzyme motor triggered by survivin mRNA. Anal Bioanal Chem 414, 6167–6175 (2022). https://doi.org/10.1007/s00216-022-04183-4

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  • DOI: https://doi.org/10.1007/s00216-022-04183-4

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