Renal clearable nanochelators for iron overload therapy

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 () and Jonghan Kim ()
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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
Hak Soo Choi: Massachusetts General Hospital and Harvard Medical School
Jonghan Kim: Northeastern University

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13143-z

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