A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo

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Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers1,2,3,4. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells5, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot. The thrombin inside is thus exposed and activates coagulation at the tumor site. Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth. The nanorobot proved safe and immunologically inert in mice and Bama miniature pigs. Our data show that DNA nanorobots represent a promising strategy for precise drug delivery in cancer therapy.

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The authors thank L.Z. Xu (Medical and Health Analysis Center of Peking University) for animal imaging and G. Z. Shi (Laboratory Animal Center of Institute of Biophysics, Chinese Academy of Sciences) for histological examination of minipigs. We also thank A. Sheftel from High Impact Editing for improving the English of the manuscript. This work was supported by grants from National Basic Research Plan of China (MoST Program 2016YFA0201601 to G.N. and B.D.), the National Natural Science Foundation of China (31730032 to G.N., 21222311, 21573051, 91127021 to B.D., the National Distinguished Young Scientists program 31325010 to G.N.), Innovation Research Group of National Natural Science Foundation (11621505 to G.N. and Yuliang Z., 21721002 to B.D.), Beijing Municipal Science & Technology Commission (Z161100000116035 to G.N., Z161100000116036 to B.D.), CAS Interdisciplinary Innovation Team to B.D., G.N. & Yuliang Z., Key Research Program of Frontier Sciences, CAS, Grant No. QYZDB-SSW-SLH029 to B.D. and US National Institute of Health Director's Transformative Research Award (R01GM104960-01 to H.Y.).

Author information

Author notes

    • Suping Li
    • , Qiao Jiang
    • , Shaoli Liu
    •  & Yinlong Zhang

    These authors contributed equally to this work.


  1. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, China, Beijing, China.

    • Suping Li
    • , Qiao Jiang
    • , Shaoli Liu
    • , Yinlong Zhang
    • , Yanhua Tian
    • , Chen Song
    • , Jing Wang
    • , Yiguo Zou
    • , Guangjun Nie
    • , Baoquan Ding
    •  & Yuliang Zhao
  2. University of Chinese Academy of Sciences, Beijing, China.

    • Suping Li
    • , Shaoli Liu
    • , Guangjun Nie
    • , Baoquan Ding
    •  & Yuliang Zhao
  3. College of Pharmaceutical Science, Jilin University, Changchun, China.

    • Yinlong Zhang
  4. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.

    • Yanhua Tian
  5. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

    • Gregory J Anderson
  6. Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.

    • Jing-Yan Han
  7. School of Molecular Sciences, Center for Molecular Design and Biomimetics; School of Life Sciences, Center for Immunotherapy, Vaccines, and Virotherapy at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.

    • Yung Chang
    • , Yan Liu
    •  & Hao Yan
  8. Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

    • Chen Zhang
    •  & Guangbiao Zhou
  9. Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.

    • Liang Chen


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Suping L., Q.J., Shaoli L., Yinlong Z., Y.T., C.S., B.D., Yuliang Z. and G.N. conceived and designed the experiments. Suping L., Q.J., Shaoli L., Yinlong Z., C.S., Y.T. and C.Z. performed the experiments. Y.T., C.S., H.Y., B.D., Yinlong Z. and G.N. collected and analyzed the data. J.W., G.A., J.H., Yiguo Z., Y.C., Y.L., L.C., G.-B.Z., G.Z. and C.Z. provided suggestions and technical support on the project. H.Y., B.D., Yuliang Z., and G.N. supervised the project. Suping L., Q.J., H.Y., B.D. and G.N. wrote the manuscript. All authors discussed the results and commented on the manuscript.

Competing interests

An international provisional patent has been filed based on this work.

Corresponding authors

Correspondence to Guangjun Nie or Hao Yan or Baoquan Ding or Yuliang Zhao.

Supplementary information

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    Supplementary Figures 1–28, Supplementary Tables 1–3, Supplementary Note 1

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