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A 3,2-Hydroxypyridinone-based Decorporation Agent that Removes Uranium from Bones In Vivo

Author

Listed:
  • Xiaomei Wang

    (Soochow University
    University of Chinese Academy of Sciences)

  • Xing Dai

    (Soochow University)

  • Cen Shi

    (Soochow University)

  • Jianmei Wan

    (Soochow University)

  • Mark A. Silver

    (Soochow University)

  • Linjuan Zhang

    (University of Chinese Academy of Sciences)

  • Lanhua Chen

    (Soochow University)

  • Xuan Yi

    (Soochow University)

  • Bizheng Chen

    (Soochow University)

  • Duo Zhang

    (Soochow University)

  • Kai Yang

    (Soochow University)

  • Juan Diwu

    (Soochow University)

  • Jianqiang Wang

    (University of Chinese Academy of Sciences)

  • Yujie Xu

    (Soochow University)

  • Ruhong Zhou

    (Soochow University
    Columbia University)

  • Zhifang Chai

    (Soochow University)

  • Shuao Wang

    (Soochow University)

Abstract

Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands. This is further revealed by the first principles calculation analysis on bonding between the ligand and uranium. Both in vitro uranium removal assay and in vivo decorporation experiments with mice show that 5LIO-1-Cm-3,2-HOPO can remove uranium from kidneys and bones with high efficiencies, while the decorporation efficiency is nearly independent of the treatment time. Moreover, this ligand shows a high oral decorporation efficiency, making it attractive for practical applications.

Suggested Citation

  • Xiaomei Wang & Xing Dai & Cen Shi & Jianmei Wan & Mark A. Silver & Linjuan Zhang & Lanhua Chen & Xuan Yi & Bizheng Chen & Duo Zhang & Kai Yang & Juan Diwu & Jianqiang Wang & Yujie Xu & Ruhong Zhou & Z, 2019. "A 3,2-Hydroxypyridinone-based Decorporation Agent that Removes Uranium from Bones In Vivo," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10276-z
    DOI: 10.1038/s41467-019-10276-z
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    Cited by:

    1. Dengqin Zhong & Ruiyun Wang & Hongjing Zhang & Mengmeng Wang & Xuxia Zhang & Honghong Chen, 2023. "Induction of lysosomal exocytosis and biogenesis via TRPML1 activation for the treatment of uranium-induced nephrotoxicity," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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