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Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Am. Chem. Soc. 2023, 145, 9, 5447-5455
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Modular DNA-Origami-Based Nanoarrays Enhance Cell Binding Affinity through the “Lock-and-Key” Interaction

  • Miao Mao
    Miao Mao
    School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China
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  • , 
  • Zhun Lin
    Zhun Lin
    School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China
    More by Zhun Lin
  • , 
  • Liang Chen
    Liang Chen
    School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China
    More by Liang Chen
  • , 
  • Zhengyu Zou
    Zhengyu Zou
    Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
    More by Zhengyu Zou
  • , 
  • Jie Zhang
    Jie Zhang
    School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China
    More by Jie Zhang
  • , 
  • Quanhao Dou
    Quanhao Dou
    Joint Laboratory of Optofluidic Technology and Systems, National Center for International Research on Green Optoelectronics, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou, Guangdong 510006, China
    More by Quanhao Dou
  • , 
  • Jiacheng Wu
    Jiacheng Wu
    School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China
    More by Jiacheng Wu
  • , 
  • Jinglin Chen
    Jinglin Chen
    School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China
    More by Jinglin Chen
  • , 
  • Minhao Wu
    Minhao Wu
    Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China
    More by Minhao Wu
  • , 
  • Li Niu
    Li Niu
    Center for Advanced Analytical Science, School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou, Guangdong 510006, China
    More by Li Niu
    Orcidhttps://orcid.org/0000-0003-3652-2903
  • , 
  • Chunhai Fan
    Chunhai Fan
    School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
    More by Chunhai Fan
    Orcidhttps://orcid.org/0000-0002-7171-7338
  • , and 
  • Yuanqing Zhang*
    Yuanqing Zhang
    School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China
    *Email: [email protected]
    More by Yuanqing Zhang
    Orcidhttps://orcid.org/0000-0002-8761-5328
Cite this: J. Am. Chem. Soc. 2023, 145, 9, 5447–5455
Publication Date (Web):February 22, 2023
https://doi.org/10.1021/jacs.2c13825
Copyright © 2023 American Chemical Society
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    Abstract

    Abstract Image

    Surface proteins of cells are generally recognized through receptor–ligand interactions (RLIs) in disease diagnosis, but their nonuniform spatial distribution and higher-order structure lead to low binding affinity. Constructing nanotopologies that match the spatial distribution of membrane proteins to improve the binding affinity remains a challenge. Inspired by the multiantigen recognition of immune synapses, we developed modular DNA-origami-based nanoarrays with multivalent aptamers. By adjusting the valency and interspacing of the aptamers, we constructed specific nanotopology to match the spatial distribution of target protein clusters and avoid potential steric hindrance. We found that the nanoarrays significantly enhanced the binding affinity of target cells and synergistically recognized low-affinity antigen-specific cells. In addition, DNA nanoarrays used for the clinical detection of circulating tumor cells successfully verified their precise recognition ability and high-affinity RLIs. Such nanoarrays will further promote the potential application of DNA materials in clinical detection and even cell membrane engineering.

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.2c13825.

    • Experimental materials and procedures, AFM images, agarose gel images, DNA origami stability and biocompatibility detection, flow cytometry analysis, fluorescence microscopy images; oligonucleotide sequences used, dissociation kinetics data, and additional references (PDF)

    • Sequences of unmodified staple strands for triangular DNA origami construction (XLSX)

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    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 3 publications.

    1. Leoni Abendstein, Willem E. M. Noteborn, Luc S. Veenman, Douwe J. Dijkstra, Fleur S. van de Bovenkamp, Leendert A. Trouw, Thomas H. Sharp. DNA Nanostructure-Templated Antibody Complexes Provide Insights into the Geometric Requirements of Human Complement Cascade Activation. Journal of the American Chemical Society 2024, Article ASAP.
    2. Xiaoxue Hu, Hongli Chi, Xiaoyi Fu, Jinling Chen, Linying Dong, Shiqi Jiang, Yan Li, Jingyi Chen, Ming Cheng, Qianhao Min, Ye Tian, Penghui Zhang. Tunable Multivalent Aptamer-Based DNA Nanostructures To Regulate Multiheteroreceptor-Mediated Tumor Recognition. Journal of the American Chemical Society 2024, 146 (4) , 2514-2523. https://doi.org/10.1021/jacs.3c10704
    3. Weijun Wang, Mengling Lin, Yan-Ru Chen, Wenqing Wang, Jinrui Lv, Yaxin Chen, Hongwei Yin, Zhifa Shen, Zai-Sheng Wu. Y-Shaped Backbone-Rigidified DNA Tiles for the Construction of Supersized Nondeformable Tetrahedrons for Precise Cancer Therapies. Analytical Chemistry 2024, 96 (4) , 1488-1497. https://doi.org/10.1021/acs.analchem.3c03923
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