Renal clearable nanochelators for iron overload therapy

Citation:

H. Kang, M. Han, J. Xue, Y. Baek, J. Chang, S. Hu, H. Nam, M. J. Jo, G. El Fakhri, M. P. Hutchens, H. S. Choi, and J. Kim. 2019. “Renal clearable nanochelators for iron overload therapy.” Nat Commun, 10, Pp. 5134.

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.

Notes:

Kang, HomanHan, MuruiXue, JieBaek, YoonjiChang, JuOaeHu, ShuangNam, HaYoungJo, Min JooEl Fakhri, GeorgesHutchens, Michael PChoi, Hak SooKim, JonghanengR01 HL143020/HL/NHLBI NIH HHS/R01 EB022230/EB/NIBIB NIH HHS/U54 HL119145/HL/NHLBI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tEnglandNat Commun. 2019 Nov 13;10(1):5134. doi: 10.1038/s41467-019-13143-z.