PMID- 31723130
OWN - NLM
STAT- MEDLINE
DCOM- 20200228
LR  - 20231019
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 10
IP  - 1
DP  - 2019 Nov 13
TI  - Renal clearable nanochelators for iron overload therapy.
PG  - 5134
LID - 10.1038/s41467-019-13143-z [doi]
LID - 5134
AB  - 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.
FAU - Kang, Homan
AU  - Kang H
AUID- ORCID: 0000-0002-0732-9779
AD  - Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General 
      Hospital and Harvard Medical School, Boston, MA, 02114, USA.
FAU - Han, Murui
AU  - Han M
AD  - Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 
      02115, USA.
FAU - Xue, Jie
AU  - Xue J
AD  - Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 
      02115, USA.
FAU - Baek, Yoonji
AU  - Baek Y
AD  - Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General 
      Hospital and Harvard Medical School, Boston, MA, 02114, USA.
FAU - Chang, JuOae
AU  - Chang J
AD  - Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 
      02115, USA.
FAU - Hu, Shuang
AU  - Hu S
AD  - Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General 
      Hospital and Harvard Medical School, Boston, MA, 02114, USA.
FAU - Nam, HaYoung
AU  - Nam H
AD  - Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 
      02115, USA.
FAU - Jo, Min Joo
AU  - Jo MJ
AD  - Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General 
      Hospital and Harvard Medical School, Boston, MA, 02114, USA.
FAU - El Fakhri, Georges
AU  - El Fakhri G
AD  - Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General 
      Hospital and Harvard Medical School, Boston, MA, 02114, USA.
FAU - Hutchens, Michael P
AU  - Hutchens MP
AUID- ORCID: 0000-0001-8583-1812
AD  - Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 
      Portland, OR, 97239, USA.
AD  - Portland Veterans Affairs Medical Center, Portland, OR, 97239, USA.
FAU - Choi, Hak Soo
AU  - Choi HS
AUID- ORCID: 0000-0002-7982-6483
AD  - Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General 
      Hospital and Harvard Medical School, Boston, MA, 02114, USA. 
      hchoi12@mgh.harvard.edu.
FAU - Kim, Jonghan
AU  - Kim J
AD  - Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, 
      02115, USA. j.kim@neu.edu.
LA  - eng
GR  - I01 BX004288/BX/BLRD VA/United States
GR  - R01 EB022230/EB/NIBIB NIH HHS/United States
GR  - R01 HL143020/HL/NHLBI NIH HHS/United States
GR  - U54 HL119145/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191113
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Iron Chelating Agents)
RN  - J06Y7MXW4D (Deferoxamine)
SB  - IM
MH  - Animals
MH  - Deferoxamine/pharmacokinetics/therapeutic use/toxicity
MH  - Iron Chelating Agents/chemistry/pharmacology/*therapeutic use
MH  - Iron Overload/*drug therapy
MH  - Kidney/*pathology
MH  - Male
MH  - Mice
MH  - Nanoparticles/*chemistry/toxicity/ultrastructure
MH  - Tissue Distribution
PMC - PMC6853917
COIS- The authors declare no competing interests.
EDAT- 2019/11/15 06:00
MHDA- 2020/02/29 06:00
PMCR- 2019/11/13
CRDT- 2019/11/15 06:00
PHST- 2019/06/23 00:00 [received]
PHST- 2019/10/22 00:00 [accepted]
PHST- 2019/11/15 06:00 [entrez]
PHST- 2019/11/15 06:00 [pubmed]
PHST- 2020/02/29 06:00 [medline]
PHST- 2019/11/13 00:00 [pmc-release]
AID - 10.1038/s41467-019-13143-z [pii]
AID - 13143 [pii]
AID - 10.1038/s41467-019-13143-z [doi]
PST - epublish
SO  - Nat Commun. 2019 Nov 13;10(1):5134. doi: 10.1038/s41467-019-13143-z.