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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Data availability

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

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. 1.

    Bellomo, R., Kellum, J. A. & Ronco, C. Acute kidney injury. Lancet 380, 756–766 (2012).

  2. 2.

    Chawla, L. S., Eggers, P. W., Star, R. A. & Kimmel, P. L. Acute kidney injury and chronic kidney disease as interconnected syndromes. N. Engl. J. Med. 371, 58–66 (2014).

  3. 3.

    Lewington, A. J. P., Cerda, J. & Mehta, R. L. Raising awareness of acute kidney injury: a global perspective of a silent killer. Kidney Int. 84, 457–467 (2013).

  4. 4.

    VA/NIH Acute Renal Failure Trial Network Intensity of renal support in critically ill patients with acute kidney injury. N. Engl. J. Med. 359, 7–20 (2008).

  5. 5.

    Tepel, M. et al. Prevention of radiographic-contrast-agent–induced reductions in renal function by acetylcysteine. N. Engl. J. Med. 343, 180–184 (2000).

  6. 6.

    Fishbane, S. N-acetylcysteine in the prevention of contrast-induced nephropathy. Clin. J. Am. Soc. Nephrol. 3, 281–287 (2008).

  7. 7.

    Wagner, V., Dullaart, A., Bock, A.-K. & Zweck, A. The emerging nanomedicine landscape. Nat. Biotechnol. 24, 1211–1217 (2006).

  8. 8.

    Peer, D. et al. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotech. 2, 751–760 (2007).

  9. 9.

    Sun, W. J. et al. Cocoon-like self-degradable DNA nanoclew for anticancer drug delivery. J. Am. Chem. Soc. 136, 14722–14725 (2014).

  10. 10.

    Min, Y., Caster, J. M., Eblan, M. J. & Wang, A. Z. Clinical translation of nanomedicine. Chem. Rev. 115, 11147–11190 (2015).

  11. 11.

    Arai, S. et al. Apoptosis inhibitor of macrophage protein enhances intraluminal debris clearance and ameliorates acute kidney injury in mice. Nat. Med. 22, 183–193 (2016).

  12. 12.

    Kamaly, N., He, J. C., Ausiello, D. A. & Farokhzad, O. C. Nanomedicines for renal disease: current status and future applications. Nat. Rev. Nephrol. 12, 738–753 (2016).

  13. 13.

    Pelaz, B. et al. Diverse applications of nanomedicine. ACS Nano 11, 2313–2381 (2017).

  14. 14.

    Alidori, S. et al. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury. Sci. Transl. Med. 8, 331ra339 (2016).

  15. 15.

    Sun, C. J. et al. Controlling assembly of paired gold clusters within apoferritin nanoreactor for in vivo kidney targeting and biomedical imaging. J. Am. Chem. Soc. 133, 8617–8624 (2011).

  16. 16.

    Choi, C. H. J., Zuckerman, J. E., Webster, P. & Davis, M. E. Targeting kidney mesangium by nanoparticles of defined size. Proc. Natl Acad. Sci. USA 108, 6656–6661 (2011).

  17. 17.

    Manne, N. et al. Cerium oxide nanoparticles attenuate acute kidney injury induced by intra-abdominal infection in Sprague-Dawley rats. J. Nanobiotechnol. 13, 75 (2015).

  18. 18.

    Zhang, H. et al. Eupafolin nanoparticle improves acute renal injury induced by LPS through inhibiting ROS and inflammation. Biomed. Pharmacother. 85, 704–711 (2017).

  19. 19.

    Pinheiro, A. V., Han, D., Shih, W. M. & Yan, H. Challenges and opportunities for structural DNA nanotechnology. Nat. Nanotech. 6, 763–772 (2011).

  20. 20.

    Seeman, N. C. Nanomaterials based on DNA. Annu. Rev. Biochem. 79, 65–87 (2010).

  21. 21.

    Zhang, F. et al. Complex wireframe DNA origami nanostructures with multi-arm junction vertices. Nat. Nanotech. 10, 779–784 (2015).

  22. 22.

    Li, J. et al. Self-assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory CpG oligonucleotides. ACS Nano 5, 8783–8789 (2011).

  23. 23.

    Mei, Q. et al. Stability of DNA origami nanoarrays in cell lysate. Nano Lett. 11, 1477–1482 (2011).

  24. 24.

    Hahn, J., Wickham, S. F., Shih, W. M. & Perrault, S. D. Addressing the instability of DNA nanostructures in tissue culture. ACS Nano 8, 8765–8775 (2014).

  25. 25.

    Surana, S., Shenoy, A. R. & Krishnan, Y. Designing DNA nanodevices for compatibility with the immune system of higher organisms. Nat. Nanotech. 10, 741–747 (2015).

  26. 26.

    Lee, H. et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat. Nanotech. 7, 389–393 (2012).

  27. 27.

    Zhu, G. et al. Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics. Proc. Natl Acad. Sci. USA 110, 7998–8003 (2013).

  28. 28.

    Torring, T., Helmig, S., Ogilby, P. R. & Gothelf, K. V. Singlet oxygen in DNA nanotechnology. Acc. Chem. Res. 47, 1799–1806 (2014).

  29. 29.

    Chen, Y.-J., Groves, B., Muscat, R. A. & Seelig, G. DNA nanotechnology from the test tube to the cell. Nat. Nanotech. 10, 748–760 (2015).

  30. 30.

    Chao, J. et al. Hetero-assembly of gold nanoparticles on a DNA origami template. Sci. China Chem. 59, 730–734 (2016).

  31. 31.

    Du, Y. et al. DNA-nanostructure–gold-nanorod hybrids for enhanced in vivo optoacoustic imaging and photothermal therapy. Adv. Mater. 28, 10000–10007 (2016).

  32. 32.

    Li, J., Green, A. A., Yan, H. & Fan, C. H. Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation. Nat. Chem. 9, 1056–1067 (2017).

  33. 33.

    Hu, Q., Li, H., Wang, L., Gu, H. & Fan, C. DNA nanotechnology-enabled drug delivery systems. Chem. Rev. https://doi.org/10.1021/acs.chemrev.7b00663 (2018).

  34. 34.

    Li, S. et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat. Biotechnol. 36, 258–264 (2018).

  35. 35.

    Zhang, Q. et al. DNA origami as an in vivo drug delivery vehicle for cancer therapy. ACS Nano 8, 6633–6643 (2014).

  36. 36.

    Jiang, D., England, C. G. & Cai, W. DNA nanomaterials for preclinical imaging and drug delivery. J. Control. Release 239, 27–38 (2016).

  37. 37.

    Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006).

  38. 38.

    Fu, J., Liu, M., Liu, Y., Woodbury, N. W. & Yan, H. Interenzyme substrate diffusion for an enzyme cascade organized on spatially addressable DNA nanostructures. J. Am. Chem. Soc. 134, 5516–5519 (2012).

  39. 39.

    Makarova, K. S., Wolf, Y. I. & Koonin, E. V. Comparative genomics of defense systems in archaea and bacteria. Nucleic Acids Res. 41, 4360–4377 (2013).

  40. 40.

    Lin, M. et al. Programmable engineering of a biosensing interface with tetrahedral DNA nanostructures for ultrasensitive DNA detection. Angew. Chem. Int. Ed. Engl. 54, 2151–2155 (2015).

  41. 41.

    Jiang, D. et al. Multiple-armed tetrahedral DNA nanostructures for tumor-targeting, dual-modality in vivo imaging. ACS Appl. Mater. Interfaces 8, 4378–4384 (2016).

  42. 42.

    Keum, J.-W. & Bermudez, H. Enhanced resistance of DNA nanostructures to enzymatic digestion. Chem. Commun. 0, 7036–7038 (2009).

  43. 43.

    Yamamoto, Y., Nagasaki, Y., Kato, Y., Sugiyama, Y. & Kataoka, K. Long-circulating poly(ethylene glycol)-poly(d,l-lactide) block copolymer micelles with modulated surface charge. J. Control. Release 77, 27–38 (2001).

  44. 44.

    Alexis, F., Pridgen, E., Molnar, L. K. & Farokhzad, O. C. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol. Pharm. 5, 505–515 (2008).

  45. 45.

    Blanco, E., Shen, H. & Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33, 941–951 (2015).

  46. 46.

    Albanese, A., Tang, P. S. & Chan, W. C. W. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu. Rev. Biomed. Eng. 14, 1–16 (2012).

  47. 47.

    Du, B. J. et al. Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime. Nat. Nanotech. 12, 1096–1102 (2017).

  48. 48.

    Lacerda, L. et al. Dynamic imaging of functionalized multi-walled carbon nanotube systemic circulation and urinary excretion. Adv. Mater. 20, 225-230 (2008).

  49. 49.

    Ruggiero, A. et al. Paradoxical glomerular filtration of carbon nanotubes. Proc. Natl Acad. Sci. USA 107, 12369–12374 (2010).

  50. 50.

    Key, J. et al. Soft discoidal polymeric nanoconstructs resist macrophage uptake and enhance vascular targeting in tumors. ACS Nano 9, 11628–11641 (2015).

  51. 51.

    Williams, R. M. et al. Mesoscale nanoparticles selectively target the renal proximal tubule epithelium. Nano Lett. 15, 2358–2364 (2015).

  52. 52.

    Boutaud, O. et al. Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure. Proc. Natl Acad. Sci. USA 107, 2699–2704 (2010).

  53. 53.

    Singh, A. P. et al. Animal models of acute renal failure. Pharmacol. Rep. 64, 31–44 (2012).

  54. 54.

    Huang, H. et al. A porphyrin–PEG polymer with rapid renal clearance. Biomaterials 76, 25–32 (2016).

  55. 55.

    Nath, K. A. & Norby, S. M. Reactive oxygen species and acute renal failure. Am. J. Med. 109, 665–678 (2000).

  56. 56.

    Valko, M. et al. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 39, 44–84 (2007).

  57. 57.

    Hemnani, T. & Parihar, M. Reactive oxygen species and oxidative DNA damage. Indian J. Physiol. Pharmacol. 42, 440–452 (1998).

  58. 58.

    Shyu, K. G., Cheng, J. J. & Kuan, P. Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. J. Am. Coll. Cardiol. 40, 1383–1388 (2002).

  59. 59.

    Hofman, M. et al. 68Ga-EDTA PET/CT imaging and plasma clearance for glomerular filtration rate quantification: comparison to conventional 51Cr-EDTA. J. Nucl. Med. 56, 405–409 (2015).

  60. 60.

    Hofman, M. S. & Hicks, R. J. Gallium-68 EDTA PET/CT for renal imaging. Semin. Nucl. Med. 46, 448–461 (2016).

  61. 61.

    Nair, A. B. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 7, 27–31 (2016).

  62. 62.

    Uchino, S. et al. Acute renal failure in critically ill patients—a multinational, multicenter study. J. Am. Med. Assoc. 294, 813–818 (2005).

  63. 63.

    Cadet, J. & Wagner, J. R. DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation. Cold Spring Harb. Perspect. Biol. 5, a012559 (2013).

  64. 64.

    Agnihotri, N. & Mishra, P. C. Mechanism of scavenging action of N-acetylcysteine for the OH radical: a quantum computational study. J. Phys. Chem. B 113, 12096–12104 (2009).

  65. 65.

    Ponnuswamy, N. et al. Oligolysine-based coating protects DNA nanostructures from low-salt denaturation and nuclease degradation. Nat. Commun. 8, 15654 (2017).

  66. 66.

    Elbaz, J., Yin, P. & Voigt, C. A. Genetic encoding of DNA nanostructures and their self-assembly in living bacteria. Nat. Commun. 7, 11179 (2016).

  67. 67.

    Praetorius, F. et al. Biotechnological mass production of DNA origami. Nature 552, 84–87 (2017).

Download references


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.

Author information

Author notes

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


  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


  1. Search for Dawei Jiang in:

  2. Search for Zhilei Ge in:

  3. Search for Hyung-Jun Im in:

  4. Search for Christopher G. England in:

  5. Search for Dalong Ni in:

  6. Search for Junjun Hou in:

  7. Search for Luhao Zhang in:

  8. Search for Christopher J. Kutyreff in:

  9. Search for Yongjun Yan in:

  10. Search for Yan Liu in:

  11. Search for Steve Y. Cho in:

  12. Search for Jonathan W. Engle in:

  13. Search for Jiye Shi in:

  14. Search for Peng Huang in:

  15. Search for Chunhai Fan in:

  16. Search for Hao Yan in:

  17. Search for Weibo Cai in:


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.

Competing interests

The authors declare no competing interests.

Corresponding authors

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

Supplementary information

  1. Supplementary Information

    Supplementary figures, tables and references.

  2. Reporting Summary

  3. Supplementary Dataset 1

    Rectangular-DON sequence and labelling.

  4. Supplementary Dataset 2

    Triangular-DON sequence and labelling.

  5. Supplementary Dataset 3

    Tubular-DON sequence and labelling.

  6. Supplementary Video 1

    PET imaging of Rec-DON in healthy mice.

  7. Supplementary Video 2

    PET imaging of Tri-DON in healthy mice.

  8. Supplementary Video 3

    PET imaging of Tub-DON in healthy mice.

  9. Supplementary Video 4

    PET imaging of Rec-DON in AKI mice.

  10. Supplementary Video 5

    Renal function evaluation using 68Ga-EDTA PET imaging.

About this article

Publication history