Renal clearable nanochelators for iron overload therapy

Homan Kang, Murui Han, Jie Xue, Yoonji Baek, Ju Oae Chang, Shuang Hu, Ha Young Nam, Min Joo Jo, Georges El Fakhri, Michael P. Hutchens, Hak Soo Choi, Jonghan Kim

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Article number5134
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Kang, H., Han, M., Xue, J., Baek, Y., Chang, J. O., Hu, S., Nam, H. Y., Jo, M. J., El Fakhri, G., Hutchens, M. P., Choi, H. S., & Kim, J. (2019). Renal clearable nanochelators for iron overload therapy. Nature communications, 10(1), [5134]. https://doi.org/10.1038/s41467-019-13143-z