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Renal clearable nanochelators for iron overload therapy

Author

Listed:
  • Homan Kang

    (Massachusetts General Hospital and Harvard Medical School)

  • Murui Han

    (Northeastern University)

  • Jie Xue

    (Northeastern University)

  • Yoonji Baek

    (Massachusetts General Hospital and Harvard Medical School)

  • JuOae Chang

    (Northeastern University)

  • Shuang Hu

    (Massachusetts General Hospital and Harvard Medical School)

  • HaYoung Nam

    (Northeastern University)

  • Min Joo Jo

    (Massachusetts General Hospital and Harvard Medical School)

  • Georges El Fakhri

    (Massachusetts General Hospital and Harvard Medical School)

  • Michael P. Hutchens

    (Oregon Health & Science University
    Portland Veterans Affairs Medical Center)

  • Hak Soo Choi

    (Massachusetts General Hospital and Harvard Medical School)

  • Jonghan Kim

    (Northeastern University)

Abstract

Iron chelators have been widely used to remove excess toxic iron from patients with secondary iron overload. However, small molecule-based iron chelators can cause adverse side effects such as infection, gastrointestinal bleeding, kidney failure, and liver fibrosis. Here we report renal clearable nanochelators for iron overload disorders. First, after a singledose intravenous injection, the nanochelator shows favorable pharmacokinetic properties, such as kidney-specific biodistribution and rapid renal excretion (>80% injected dose in 4 h), compared to native deferoxamine (DFO). Second, subcutaneous (SC) administration of nanochelators improves pharmacodynamics, as evidenced by a 7-fold increase in efficiency of urinary iron excretion compared to intravenous injection. Third, daily SC injections of the nanochelator for 5 days to iron overload mice and rats decrease iron levels in serum and liver. Furthermore, the nanochelator significantly reduces kidney damage caused by iron overload without demonstrating DFO’s own nephrotoxicity. This renal clearable nanochelator provides enhanced efficacy and safety.

Suggested Citation

  • Homan Kang & Murui Han & Jie Xue & Yoonji Baek & JuOae Chang & Shuang Hu & HaYoung Nam & Min Joo Jo & Georges El Fakhri & Michael P. Hutchens & Hak Soo Choi & Jonghan Kim, 2019. "Renal clearable nanochelators for iron overload therapy," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13143-z
    DOI: 10.1038/s41467-019-13143-z
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    Cited by:

    1. Minfeng Huo & Zhimin Tang & Liying Wang & Linlin Zhang & Haiyan Guo & Yu Chen & Ping Gu & Jianlin Shi, 2022. "Magnesium hexacyanoferrate nanocatalysts attenuate chemodrug-induced cardiotoxicity through an anti-apoptosis mechanism driven by modulation of ferrous iron," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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