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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Kang H,Han M,Xue J,Baek Y,Chang J,Hu S,Nam H,Jo MJ,El Fakhri G,Hutchens MP,Choi HS,Kim Jdoi
10.1038/s41467-019-13143-zsubject
Has Abstractpub_date
2019-11-13 00:00:00pages
5134issue
1issn
2041-1723pii
10.1038/s41467-019-13143-zjournal_volume
10pub_type
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