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Renal clearable nanochelators for iron overload therapy

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 na...

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Autores principales: Kang, Homan, Han, Murui, Xue, Jie, Baek, Yoonji, Chang, JuOae, Hu, Shuang, Nam, HaYoung, Jo, Min Joo, El Fakhri, Georges, Hutchens, Michael P., Choi, Hak Soo, Kim, Jonghan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853917/
https://www.ncbi.nlm.nih.gov/pubmed/31723130
http://dx.doi.org/10.1038/s41467-019-13143-z
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author Kang, Homan
Han, Murui
Xue, Jie
Baek, Yoonji
Chang, JuOae
Hu, Shuang
Nam, HaYoung
Jo, Min Joo
El Fakhri, Georges
Hutchens, Michael P.
Choi, Hak Soo
Kim, Jonghan
author_facet Kang, Homan
Han, Murui
Xue, Jie
Baek, Yoonji
Chang, JuOae
Hu, Shuang
Nam, HaYoung
Jo, Min Joo
El Fakhri, Georges
Hutchens, Michael P.
Choi, Hak Soo
Kim, Jonghan
author_sort Kang, Homan
collection PubMed
description 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.
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spelling pubmed-68539172019-11-18 Renal clearable nanochelators for iron overload therapy Kang, Homan Han, Murui Xue, Jie Baek, Yoonji Chang, JuOae Hu, Shuang Nam, HaYoung Jo, Min Joo El Fakhri, Georges Hutchens, Michael P. Choi, Hak Soo Kim, Jonghan Nat Commun Article 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. Nature Publishing Group UK 2019-11-13 /pmc/articles/PMC6853917/ /pubmed/31723130 http://dx.doi.org/10.1038/s41467-019-13143-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kang, Homan
Han, Murui
Xue, Jie
Baek, Yoonji
Chang, JuOae
Hu, Shuang
Nam, HaYoung
Jo, Min Joo
El Fakhri, Georges
Hutchens, Michael P.
Choi, Hak Soo
Kim, Jonghan
Renal clearable nanochelators for iron overload therapy
title Renal clearable nanochelators for iron overload therapy
title_full Renal clearable nanochelators for iron overload therapy
title_fullStr Renal clearable nanochelators for iron overload therapy
title_full_unstemmed Renal clearable nanochelators for iron overload therapy
title_short Renal clearable nanochelators for iron overload therapy
title_sort renal clearable nanochelators for iron overload therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853917/
https://www.ncbi.nlm.nih.gov/pubmed/31723130
http://dx.doi.org/10.1038/s41467-019-13143-z
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