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DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury

Nature Biomedical Engineering volume 2, pages 865–877 (2018)Cite this article

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Abstract

Patients with acute kidney injury (AKI) frequently require kidney transplantation and supportive therapies, such as rehydration and dialysis. Here, we show that radiolabelled DNA origami nanostructures (DONs) with rectangular, triangular and tubular shapes accumulate preferentially in the kidneys of healthy mice and mice with rhabdomyolysis-induced AKI, and that rectangular DONs have renal-protective properties, with efficacy similar to the antioxidant N-acetylcysteine—a clinically used drug that ameliorates contrast-induced AKI and protects kidney function from nephrotoxic agents. We evaluated the biodistribution of DONs non-invasively via positron emission tomography, and the efficacy of rectangular DONs in the treatment of AKI via dynamic positron emission tomography imaging with 68Ga-EDTA, blood tests and kidney tissue staining. DNA-based nanostructures could become a source of therapeutic agents for the treatment of AKI and other renal diseases.

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Fig. 1: Preferential renal accumulation of DONs enabled protection against AKI.
Fig. 2: Biodistribution of DONs in healthy mice.
Fig. 3: Animal study design and PET imaging of 64Cu-Rec-DON in the murine model of AKI.
Fig. 4: ROS scavenging effect of DONs in vitro.
Fig. 5: Dynamic PET imaging using 68Ga-EDTA for evaluation of kidney function.
Fig. 6: Bodyweight change, and blood and kidney tissue analysis after treatment for AKI.

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The authors declare that all data supporting the findings of this study are available within the paper and its Supplementary Information.

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Acknowledgements

The authors thank J. J. Jeffery and A. M. Weichmann for help with the small-animal imaging studies. The authors are grateful for insightful input from B. Yu, R. Hernandez, S. Goel, L. Kang and E. B. Ehlerding. This work was supported in part by the University of Wisconsin–Madison, National Institutes of Health (1R01GM104960, P30CA014520 and T32CA009206), National Natural Science Foundation of China (31771036, 51703132 and 51573096), Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (2018B030308003), Fok Ying-Tong Education Foundation for Young Teachers in Higher Education Institutions of China (161032) and Basic Research Program of Shenzhen (JCYJ20170412111100742 and JCYJ20160422091238319). C.F. gratefully acknowledges the National Key R&D Program of China (2016YFA0201200), NSFC (21329501 and 21390414) and Chinese Academy of Sciences (QYZDJ-SSW-SLH031). This work is dedicated to the memory of Q. Huang, whose great insights inspired this project.

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Author notes

  1. These authors contributed equally: Dawei Jiang, Zhilei Ge, Hyung-Jun Im.

Authors and Affiliations

  1. Department of Radiology, University of Wisconsin–Madison, Madison, WI, USA

    Dawei Jiang, Hyung-Jun Im, Dalong Ni, Yongjun Yan, Steve Y. Cho & Weibo Cai

  2. Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Laboratory of Evolutionary Theranostics, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China

    Dawei Jiang & Peng Huang

  3. Biodesign Center for Molecular Design and Biomimetics, The Biodesign Institute, School of Molecular Sciences, Arizona State University, Tempe, AZ, USA

    Zhilei Ge, Yan Liu & Hao Yan

  4. School of Chemistry and Chemical Engineering, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Zhilei Ge & Chunhai Fan

  5. Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea

    Hyung-Jun Im

  6. Department of Medical Physics, University of Wisconsin–Madison, Madison, WI, USA

    Christopher G. England, Christopher J. Kutyreff, Yongjun Yan, Jonathan W. Engle & Weibo Cai

  7. Division of Physical Biology and Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China

    Junjun Hou, Luhao Zhang, Jiye Shi & Chunhai Fan

  8. Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China

    Luhao Zhang

  9. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Steve Y. Cho & Weibo Cai

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Contributions

W.C., H.Y., P.H. and C.F. conceived the idea and supervised the project. D.J., Z.G. and H.-J.I. conceived and designed the experiments. Z.G. provided the DNA nanostructures and characterization data. D.J. and H.-J.I. performed the radiolabelling, PET imaging studies, animal model establishment and treatment studies, and analysed the data. Z.G., J.H. and L.Z. performed the DON stability experiments. D.J., Z.G., H.-J.I., C.G.E., D.N. and L.Z. performed the cellular studies. C.J.K. and J.W.E. produced Cu-64. Y.Y. and S.Y.C. provided Ga-68. D.J., Z.G., H.-J.I., C.G.E., Y.L., J.S., P.H., C.F., H.Y. and W.C. prepared the manuscript.

Corresponding authors

Correspondence to Peng Huang, Chunhai Fan, Hao Yan or Weibo Cai.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Supplementary figures, tables and references.

Reporting Summary

Supplementary Dataset 1

Rectangular-DON sequence and labelling.

Supplementary Dataset 2

Triangular-DON sequence and labelling.

Supplementary Dataset 3

Tubular-DON sequence and labelling.

Supplementary Video 1

PET imaging of Rec-DON in healthy mice.

Supplementary Video 2

PET imaging of Tri-DON in healthy mice.

Supplementary Video 3

PET imaging of Tub-DON in healthy mice.

Supplementary Video 4

PET imaging of Rec-DON in AKI mice.

Supplementary Video 5

Renal function evaluation using 68Ga-EDTA PET imaging.

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Jiang, D., Ge, Z., Im, HJ. et al. DNA origami nanostructures can exhibit preferential renal uptake and alleviate acute kidney injury. Nat Biomed Eng 2, 865–877 (2018). https://doi.org/10.1038/s41551-018-0317-8

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