Abstract |
Renal fibrosis is a common progressive kidney disease, and there is a lack of efficient treatment for the condition. In this study, we designed a kidney-specific nanocomplex by forming coordination-driven assembly from catechol-derived low molecular weight chitosan (HCA-Chi), metal ions and active drug molecules. The coordination activities of various metals and ligands, cytotoxicity, immunogenicity and biodistribution of HCA-Chi were investigated. Autofluorescent doxorubicin (DOX) was selected to fabricate HCA-Chi-Cu-DOX ternary nanocomplex for investigating cellular uptake behavior, transmembrane and targeting properties. The nanodevice demonstrated satisfactory stability under normal physiological conditions and pH-responsive drug release in acidic environments. Uptake of HCA-Chi-Cu-DOX by HK-2 cells was dependent on exposure time, concentration, and temperature, and was inhibited by blockers of megalin receptor. Tissue distribution showed that HCA-Chi-Cu-DOX nanocomplex was specifically accumulated in kidney with a renal relative uptake rate (r(e)) of 25.6. When active anti- fibrosis compound emodin was installed in HCA-Chi-Zn- emodin and intravenously injected to the ureter obstructed mice, obvious attenuation of fibrotic progression was exhibited. It was concluded that HCA-Chi coordination-driven nanocomplex showed special renal targeting capacity and could be utilized to develop drug delivery systems for treating renal fibrosis.
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Authors | Hongzhi Qiao, Minjie Sun, Zhigui Su, Ying Xie, Minglei Chen, Li Zong, Yahan Gao, Huipeng Li, Jianping Qi, Qun Zhao, Xiaochen Gu, Qineng Ping |
Journal | Biomaterials
(Biomaterials)
Vol. 35
Issue 25
Pg. 7157-71
(Aug 2014)
ISSN: 1878-5905 [Electronic] Netherlands |
PMID | 24862442
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Catechols
- Doxorubicin
- Chitosan
- catechol
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Topics |
- Animals
- Catechols
(chemistry, pharmacokinetics)
- Cell Line, Tumor
- Chitosan
(chemistry, pharmacokinetics)
- Doxorubicin
(chemistry, pharmacokinetics)
- Drug Delivery Systems
(methods)
- Fibrosis
- Humans
- Kidney
(drug effects, pathology)
- Kidney Diseases
(drug therapy)
- Male
- Mice
- Mice, Inbred ICR
- Microscopy, Confocal
- Molecular Weight
- Nanoparticles
(chemistry)
- Rats
- Tissue Distribution
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