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Nano Research 2023, 16(1): 1286-1295 https://doi.org/10.1007/s12274-022-4794-4
Research Article | Issue | Published: 21 August 2022

Bispecific aptamer-initiated 3D DNA nanomotor biosensor powered by DNAzyme and entropy-driven circuit for sensitive and specificity detection of lysozyme

Show Author's Information Shuo Qi1,2,  Yuhan Sun1,2,  Xiaoze Dong1,2,  Imran Mahmood Khan1,2,  Yan Lv1,2,  Yin Zhang3,  Nuo Duan1,2,  Shijia Wu1,2,  Zhouping Wang1,2,3,4,5( )
State Key Laboratory of Food Science and Technology, International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China
School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
Key Laboratory of Meat Processing of Sichuan, Chengdu University, Chengdu 610106, China
National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
Collaborative Inno vation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China
Keywords:
specificity, bispecific aptamer, DNA rolling, DNA walking, amplification
Topics:
Nanosensors
Cite this article:
Qi S, Sun Y, Dong X, et al. Bispecific aptamer-initiated 3D DNA nanomotor biosensor powered by DNAzyme and entropy-driven circuit for sensitive and specificity detection of lysozyme. Nano Research, 2023, 16(1): 1286-1295. https://doi.org/10.1007/s12274-022-4794-4
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Abstract Full text Electronic supplementary material About this article

Dynamic DNA nanodevices have gained tremendous attention due to their extraordinary inherent functionality and advantages, however, dynamic DNA nanodevices-based biosensors are still challenging due to their high reliance on proteases and limited amplification capabilities. Herein, exploiting bispecific aptamer as initiators for the first time, we developed a three-dimensional (3D) DNA nanomotor biosensor powered by DNAzyme and entropy-driven circuit for sensitive and specific detection of lysozyme, in which walking and rolling strategies are efficiently integrated to achieve excellent signal amplification capability. Benefiting from the high selectivity of bispecific aptamer, the 3D DNA nanomotor biosensor can respond to lysozyme with high specificity and operate at high speed to release signals. The whole process is independent of protease, avoiding the influence of adverse environment on the operation stability. Under optimal conditions, it can achieve a limit of detection as low as 0.01 pg/mL with an excellent linear range of 0.05 pg/mL–500 ng/mL for lysozyme. Furthermore, the proposed strategy revealed high accuracy in the analysis of real samples, indicating a great potential for the application of nanomotor biosensors to the detection of non-nucleic acid targets.


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About this article

Bispecific aptamer-initiated 3D DNA nanomotor biosensor powered by DNAzyme and entropy-driven circuit for sensitive and specificity detection of lysozyme

Show Author's information Shuo Qi1,2, Yuhan Sun1,2, Xiaoze Dong1,2, Imran Mahmood Khan1,2, Yan Lv1,2, Yin Zhang3, Nuo Duan1,2, Shijia Wu1,2, Zhouping Wang1,2,3,4,5( )
State Key Laboratory of Food Science and Technology, International Joint Laboratory on Food Safety, Jiangnan University, Wuxi 214122, China
School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
Key Laboratory of Meat Processing of Sichuan, Chengdu University, Chengdu 610106, China
National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
Collaborative Inno vation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, Wuxi 214122, China

Abstract

Dynamic DNA nanodevices have gained tremendous attention due to their extraordinary inherent functionality and advantages, however, dynamic DNA nanodevices-based biosensors are still challenging due to their high reliance on proteases and limited amplification capabilities. Herein, exploiting bispecific aptamer as initiators for the first time, we developed a three-dimensional (3D) DNA nanomotor biosensor powered by DNAzyme and entropy-driven circuit for sensitive and specific detection of lysozyme, in which walking and rolling strategies are efficiently integrated to achieve excellent signal amplification capability. Benefiting from the high selectivity of bispecific aptamer, the 3D DNA nanomotor biosensor can respond to lysozyme with high specificity and operate at high speed to release signals. The whole process is independent of protease, avoiding the influence of adverse environment on the operation stability. Under optimal conditions, it can achieve a limit of detection as low as 0.01 pg/mL with an excellent linear range of 0.05 pg/mL–500 ng/mL for lysozyme. Furthermore, the proposed strategy revealed high accuracy in the analysis of real samples, indicating a great potential for the application of nanomotor biosensors to the detection of non-nucleic acid targets.

Keywords: specificity, bispecific aptamer, DNA rolling, DNA walking, amplification

References(52)

[1]

Seeman, N. C. DNA in a material world. Nature 2003, 421, 427–431.
DOI Google Scholar
[2]

Zhang, F.; Nangreave, J.; Liu, Y.; Yan, H. Structural DNA nanotechnology: State of the art and future perspective. J. Am. Chem. Soc. 2014, 136, 11198–11211.
DOI Google Scholar
[3]

Wang, Q.; Wang, J.; Huang, Y.; Du, Y. C.; Zhang, Y.; Cui, Y. X.; Kong, D. M. Development of the DNA-based biosensors for high performance in detection of molecular biomarkers: More rapid, sensitive, and universal. Biosens. Bioelectron. 2022, 197, 113739.
DOI Google Scholar
[4]

Libanori, A.; Chen, G. R.; Zhao, X.; Zhou, Y. H.; Chen, J. Smart textiles for personalized healthcare. Nat. Electron. 2022, 5, 142–156.
DOI Google Scholar
[5]

Chen, G. R.; Xiao, X.; Zhao, X.; Tat, T.; Bick, M.; Chen, J. Electronic textiles for wearable point-of-care systems. Chem. Rev. 2022, 122, 3259–3291.
DOI Google Scholar
[6]

Miao, P.; Tang, Y. G. DNA walking and rolling nanomachine for electrochemical detection of miRNA. Small 2020, 16, 2004518.
DOI Google Scholar
[7]

Wang, H. Z.; Zeng, J. H.; Huang, J.; Cheng, H.; Chen, B.; Hu, X.; He, X. X.; Zhou, Y.; Wang, K. M. A self-serviced-track 3D DNA walker for ultrasensitive detection of tumor exosomes by glycoprotein profiling. Angew. Chem., Int. Ed. 2022, 134, e202116932.
DOI Google Scholar
[8]

Ryssy, J.; Natarajan, A. K.; Wang, J. H.; Lehtonen, A. J.; Nguyen, M. K.; Klajn, R.; Kuzyk, A. Light-responsive dynamic DNA-origami-based plasmonic assemblies. Angew. Chem., Int. Ed. 2021, 60, 5859–5863.
DOI Google Scholar
[9]

Turek, V. A.; Chikkaraddy, R.; Cormier, S.; Stockham, B.; Ding, T.; Keyser, U. F.; Baumberg, J. J. Thermo-responsive actuation of a DNA origami flexor. Adv. Funct. Mater. 2018, 28, 1706410.
DOI Google Scholar
[10]

Suzuki, Y.; Kawamata, I.; Mizuno, K.; Murata, S. Large deformation of a DNA-origami nanoarm induced by the cumulative actuation of tension-adjustable modules. Angew. Chem., Int. Ed. 2020, 59, 6230–6234.
DOI Google Scholar
[11]

Hoffecker, I. T.; Chen, S. J.; Gådin, A.; Bosco, A.; Teixeira, A. I.; Högberg, B. Solution-controlled conformational switching of an anchored wireframe DNA nanostructure. Small 2019, 15, 1803628.
DOI Google Scholar
[12]

Kroener, F.; Heerwig, A.; Kaiser, W.; Mertig, M.; Rant, U. Electrical actuation of a DNA origami nanolever on an electrode. J. Am. Chem. Soc. 2017, 139, 16510–16513.
DOI Google Scholar
[13]

Yurke, B.; Turberfield, A. J.; Mills, A. P.; Simmel, F. C.; Neumann, J. L. A DNA-fuelled molecular machine made of DNA. Nature 2000, 406, 605–608.
DOI Google Scholar
[14]

Tian, Y.; Mao, C. D. Molecular gears:   A pair of DNA circles continuously rolls against each other. J. Am. Chem. Soc. 2004, 126, 11410–11411.
DOI Google Scholar
[15]

Thubagere, A. J.; Li, W.; Johnson, R. F.; Chen, Z. B.; Doroudi, S.; Lee, Y. L.; Izatt, G.; Wittman, S.; Srinivas, N.; Woods, D. et al. A cargo-sorting DNA robot. Science 2017, 357, eaan6558.
DOI Google Scholar
[16]

Ahmadi, Y.; Nord, A. L.; Wilson, A. J.; Hütter, C.; Schroeder, F.; Beeby, M.; Barišić, I. The Brownian and flow-driven rotational dynamics of a multicomponent DNA origami-based rotor. Small 2020, 16, 2001855.
DOI Google Scholar
[17]

Lund, K.; Manzo, A. J.; Dabby, N.; Michelotti, N.; Johnson-Buck, A.; Nangreave, J.; Taylor, S.; Pei, R. J.; Stojanovic, M. N.; Walter, N. G. et al. Molecular robots guided by prescriptive landscapes. Nature 2010, 465, 206–210.
DOI Google Scholar
[18]

Zhang, H.; Xu, X. W.; Jiang, W. An interparticle relatively motional DNA walker and its sensing application. Chem. Sci. 2020, 11, 7415–7423.
DOI Google Scholar
[19]

Zhang, X.; Wei, X. W.; Qi, J. J.; Shen, J.; Xu, J. W.; Gong, G. Y.; Wei, Y.; Yang, J.; Zhu, Q. Y.; Bai, T. T. et al. Simultaneous detection of bladder cancer exosomal microRNAs based on inorganic nanoflare and DNAzyme walker. Anal. Chem. 2022, 94, 4787–4793.
DOI Google Scholar
[20]

Jung, C.; Allen, P. B.; Ellington, A. D. A stochastic DNA walker that traverses a microparticle surface. Nat. Nanotechnol. 2016, 11, 157–163.
DOI Google Scholar
[21]

Oishi, M.; Saito, K. Simple single-legged DNA walkers at diffusion-limited nanointerfaces of gold nanoparticles driven by a DNA circuit mechanism. ACS Nano 2020, 14, 3477–3489.
DOI Google Scholar
[22]

Yang, P.; Li, Y. Y.; Mason, S. D.; Chen, F. F.; Chen, J. B.; Zhou, R. X.; Liu, J. W.; Hou, X. D.; Li, F. Concentric DNA amplifier that streamlines in-solution biorecognition and on-particle biocatalysis. Anal. Chem. 2020, 92, 3220–3227.
DOI Google Scholar
[23]

Mason, S. D.; Tang, Y. N.; Li, Y. Y.; Xie, X. Y.; Li, F. Emerging bioanalytical applications of DNA walkers. TrAC, Trends Anal. Chem. 2018, 107, 212–221.
DOI Google Scholar
[24]

Yuan, C. J.; Fang, J.; Duan, Q. Y.; Yan, Q.; Guo, J.; Yuan, T. X.; Yi, G. Two-layer three-dimensional DNA walker with highly integrated entropy-driven and enzyme-powered reactions for HIV detection. Biosens. Bioelectron. 2019, 133, 243–249.
DOI Google Scholar
[25]

Li, D. D.; Xu, Y. X.; Fan, L.; Shen, B.; Ding, X. J.; Yuan, R.; Li, X. M.; Chen, W. X. Target-driven rolling walker based electrochemical biosensor for ultrasensitive detection of circulating tumor DNA using doxorubicin@tetrahedron-Au tags. Biosens. Bioelectron. 2020, 148, 111826.
DOI Google Scholar
[26]

Yang, X. L.; Tang, Y. N.; Mason, S. D.; Chen, J. B.; Li, F. Enzyme-powered three-dimensional DNA nanomachine for DNA walking, payload release, and biosensing. ACS Nano 2016, 10, 2324–2330.
DOI Google Scholar
[27]

Qu, X. M.; Zhu, D.; Yao, G. B.; Su, S.; Chao, J.; Liu, H. J.; Zuo, X. L.; Wang, L. H.; Shi, J. Y.; Wang, L. H. et al. An exonuclease III-powered, on-particle stochastic DNA walker. Angew. Chem., Int. Ed. 2017, 56, 1855–1858.
DOI Google Scholar
[28]

Feng, C.; Wang, Z. H.; Chen, T. S.; Chen, X. X.; Mao, D. S.; Zhao, J.; Li, G. X. A dual-enzyme-assisted three-dimensional DNA walking machine using T4 polynucleotide kinase as activators and application in polynucleotide kinase assays. Anal. Chem. 2018, 90, 2810–2815.
DOI Google Scholar
[29]

Huang, W.; Zhan, D. Y.; Xie, Y. M.; Li, X.; Lai, G. S. Dual CHA-mediated high-efficient formation of a tripedal DNA walker for constructing a novel proteinase-free dual-mode biosensing strategy. Biosens. Bioelectron. 2022, 197, 113708.
DOI Google Scholar
[30]

Wei, W. T.; Lin, H.; Hao, T. T.; Wang, S.; Hu, Y. F.; Guo, Z. Y.; Luo, X. Y. DNA walker-mediated biosensor for target-triggered triple-mode detection of Vibrio parahaemolyticus. Biosens. Bioelectron. 2021, 186, 113305.
DOI Google Scholar
[31]

Yu, Y. Y.; Zhang, W. S.; Guo, Y. H.; Peng, H. P.; Zhu, M.; Miao, D. D.; Su, G. X. Engineering of exosome-triggered enzyme-powered DNA motors for highly sensitive fluorescence detection of tumor-derived exosomes. Biosens. Bioelectron. 2020, 167, 112482.
DOI Google Scholar
[32]

Yehl, K.; Mugler, A.; Vivek, S.; Liu, Y.; Zhang, Y.; Fan, M. Z.; Weeks, E. R.; Salaita, K. High-speed DNA-based rolling motors powered by RNase H. Nat. Nanotechnol. 2016, 11, 184–190.
DOI Google Scholar
[33]

Xu, Z. Q.; Chang, Y. Y.; Chai, Y. Q.; Wang, H. J.; Yuan, R. Ultrasensitive electrochemiluminescence biosensor for speedy detection of microRNA based on a DNA rolling machine and target recycling. Anal. Chem. 2019, 91, 4883–4888.
DOI Google Scholar
[34]

Li, J. M.; Johnson-Buck, A.; Yang, Y. R.; Shih, W. M.; Yan, H.; Walter, N. G. Exploring the speed limit of toehold exchange with a cartwheeling DNA acrobat. Nat. Nanotechnol. 2018, 13, 723–729.
DOI Google Scholar
[35]

Wu, N.; Wang, K.; Wang, Y. T.; Chen, M. L.; Chen, X. W.; Yang, T.; Wang, J. H. Three-dimensional DNA nanomachine biosensor by integrating DNA walker and rolling machine cascade amplification for ultrasensitive detection of cancer-related gene. Anal. Chem. 2020, 92, 11111–11118.
DOI Google Scholar
[36]

Miao, P.; Chai, H.; Tang, Y. G. DNA hairpins and dumbbell-wheel transitions amplified walking nanomachine for ultrasensitive nucleic acid detection. ACS Nano 2022, 16, 4726–4733.
DOI Google Scholar
[37]

Qi, S.; Duan, N.; Khan, I. M.; Dong, X. Z.; Zhang, Y.; Wu, S. J.; Wang, Z. P. Strategies to manipulate the performance of aptamers in SELEX, post-SELEX and microenvironment. Biotechnol. Adv. 2022, 55, 107902.
DOI Google Scholar
[38]

Qi, S.; Duan, N.; Sun, Y. H.; Zhou, Y.; Ma, P. F.; Wu, S. J.; Wang, Z. P. High-affinity aptamer of allergen β-lactoglobulin: Selection, recognition mechanism and application. Sensor. Actuat. B:Chem. 2021, 340, 129956.
DOI Google Scholar
[39]

Wang, L. P.; Liang, H.; Sun, J.; Liu, Y. C.; Li, J. Y.; Li, J. Y.; Li, J.; Yang, H. H. Bispecific aptamer induced artificial protein-pairing: A strategy for selective inhibition of receptor function. J. Am. Chem. Soc. 2019, 141, 12673–12681.
DOI Google Scholar
[40]

Miao, Y. Y.; Gao, Q. Q.; Mao, M. H.; Zhang, C.; Yang, L. Q.; Yang, Y.; Han, D. Bispecific aptamer chimeras enable targeted protein degradation on cell membranes. Angew. Chem., Int. Ed. 2021, 60, 11267–11271.
DOI Google Scholar
[41]

Zhu, C.; Li, L. S.; Wang, Z. J.; Irfan, M.; Qu, F. Recent advances of aptasensors for exosomes detection. Biosens. Bioelectron. 2020, 160, 112213.
DOI Google Scholar
[42]

Ueki, R.; Atsuta, S.; Ueki, A.; Sando, S. Nongenetic reprogramming of the ligand specificity of growth factor receptors by bispecific DNA aptamers. J. Am. Chem. Soc. 2017, 139, 6554–6557.
DOI Google Scholar
[43]

Yang, Y.; Sun, X. Q.; Xu, J.; Cui, C.; Safari Yazd, H.; Pan, X. S.; Zhu, Y. J.; Chen, X. G.; Li, X. W.; Li, J. et al. Circular bispecific aptamer-mediated artificial intercellular recognition for targeted T cell immunotherapy. ACS Nano 2020, 14, 9562–9571.
DOI Google Scholar
[44]

Liu, X. W.; Yan, H.; Liu, Y.; Chang, Y. Targeted cell−cell interactions by DNA nanoscaffold-templated multivalent bispecific aptamers. Small 2011, 7, 1673–1682.
DOI Google Scholar
[45]

Leśnierowski, G.; Yang, T. Y. Lysozyme and its modified forms: A critical appraisal of selected properties and potential. Trends Food Sci. Technol. 2021, 107, 333–342.
DOI Google Scholar
[46]

Melinte, G.; Selvolini, G.; Cristea, C.; Marrazza, G. Aptasensors for lysozyme detection: Recent advances. Talanta 2021, 226, 122169.
DOI Google Scholar
[47]

Cox, J. C.; Ellington, A. D. Automated selection of anti-protein aptamers. Biorg. Med. Chem. 2001, 9, 2525–2531.
DOI Google Scholar
[48]

Zou, M. J.; Chen, Y.; Xu, X.; Huang, H. D.; Liu, F.; Li, N. The homogeneous fluorescence anisotropic sensing of salivary lysozyme using the 6-carboxyfluorescein-labeled DNA aptamer. Biosens. Bioelectron. 2012, 32, 148–154.
DOI Google Scholar
[49]

Wang, B. B.; Zhao, X.; Chen, L. J.; Yang, C.; Yan, X. P. Functionalized persistent luminescence nanoparticle-based aptasensor for autofluorescence-free determination of kanamycin in food samples. Anal. Chem. 2021, 93, 2589–2595.
DOI Google Scholar
[50]

Han, J. P.; Cui, Y. C.; Li, F.; Gu, Z.; Yang, D. Y. Responsive disassembly of nucleic acid nanocomplex in cells for precision medicine. Nano Today 2021, 39, 101160.
DOI Google Scholar
[51]

Han, J. P.; Cui, Y. C.; Gu, Z.; Yang, D. Y. Controllable assembly/disassembly of polyphenol-DNA nanocomplex for cascade-responsive drug release in cancer cells. Biomaterials 2021, 273, 120846.
DOI Google Scholar
[52]

Jia, H. R.; Zhang, Z.; Fang, X.; Jiang, M.; Chen, M.; Chen, S.; Gu, K.; Luo, Z.; Wu, F. G.; Tan, W. Recent advances of cell surface modification based on aptamers. Mater. Today Nano 2022, 18, 100188.
DOI Google Scholar
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Publication history
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Acknowledgements

Publication history

Received: 24 June 2022
Revised: 18 July 2022
Accepted: 18 July 2022
Published: 21 August 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was partly funded by the National Natural Science Foundation of China (Nos. 31871881 and 31871721), the National First-class Discipline Program of Food Science and Technology (No. JUFSTR20180303), and the National High-Level Personnel of Special Support Program (No. W03020371).

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