Renal clearable nanochelators for iron overload therapy.

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 Commun

journal_title

Nature communications

authors

Kang H,Han M,Xue J,Baek Y,Chang J,Hu S,Nam H,Jo MJ,El Fakhri G,Hutchens MP,Choi HS,Kim J

doi

10.1038/s41467-019-13143-z

subject

Has Abstract

pub_date

2019-11-13 00:00:00

pages

5134

issue

1

issn

2041-1723

pii

10.1038/s41467-019-13143-z

journal_volume

10

pub_type

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