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Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes

Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin-methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highl...

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Autores principales: Wu, Lin, Chen, Mingyu, Mao, Huijuan, Wang, Ningning, Zhang, Bo, Zhao, Xiufen, Qian, Jun, Xing, Changying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360426/
https://www.ncbi.nlm.nih.gov/pubmed/28259932
http://dx.doi.org/10.3892/ijmm.2017.2902
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author Wu, Lin
Chen, Mingyu
Mao, Huijuan
Wang, Ningning
Zhang, Bo
Zhao, Xiufen
Qian, Jun
Xing, Changying
author_facet Wu, Lin
Chen, Mingyu
Mao, Huijuan
Wang, Ningning
Zhang, Bo
Zhao, Xiufen
Qian, Jun
Xing, Changying
author_sort Wu, Lin
collection PubMed
description Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin-methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highly express the specific neonatal Fc receptor (FcRn) of albumin. Bovine serum albumin (BSA) was labeled with a fluorescent dye and linked with modified MP via an amide bond. The outcome nanoparticle named BSA633-MP showed a uniform size with a diameter of approximately 10 nm and contained 12 drug molecules on average. The nanoconjugates were found to be stable at pH 7.4 and acid-sensitive at pH 4.0, with approximately 72% release of the MP drug after 48 h of incubation. The nanoparticle demonstrated a 36-fold uptake in receptor-specific cellular delivery in the FcRn-expressing human podocytes compared to the uptake in the non-FcRn-expressing control cells. Co-localization further confirmed that uptake of the nanoconjugates involved receptor-mediated endocytosis followed by lysosome associated transportation. In vitro cellular experiments indicated that the BSA633-MP ameliorated puromycin aminonucleoside-induced podocyte apoptosis. Moreover, in vivo fluorescence molecular imaging showed that BSA633-MP was mainly accumulated in the liver and kidney after intravenous dosing for 24 h. Collectively, this study may provide an approach for the effective and safe therapy of nephrotic syndrome.
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spelling pubmed-53604262017-04-10 Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes Wu, Lin Chen, Mingyu Mao, Huijuan Wang, Ningning Zhang, Bo Zhao, Xiufen Qian, Jun Xing, Changying Int J Mol Med Articles Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin-methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highly express the specific neonatal Fc receptor (FcRn) of albumin. Bovine serum albumin (BSA) was labeled with a fluorescent dye and linked with modified MP via an amide bond. The outcome nanoparticle named BSA633-MP showed a uniform size with a diameter of approximately 10 nm and contained 12 drug molecules on average. The nanoconjugates were found to be stable at pH 7.4 and acid-sensitive at pH 4.0, with approximately 72% release of the MP drug after 48 h of incubation. The nanoparticle demonstrated a 36-fold uptake in receptor-specific cellular delivery in the FcRn-expressing human podocytes compared to the uptake in the non-FcRn-expressing control cells. Co-localization further confirmed that uptake of the nanoconjugates involved receptor-mediated endocytosis followed by lysosome associated transportation. In vitro cellular experiments indicated that the BSA633-MP ameliorated puromycin aminonucleoside-induced podocyte apoptosis. Moreover, in vivo fluorescence molecular imaging showed that BSA633-MP was mainly accumulated in the liver and kidney after intravenous dosing for 24 h. Collectively, this study may provide an approach for the effective and safe therapy of nephrotic syndrome. D.A. Spandidos 2017-04 2017-02-21 /pmc/articles/PMC5360426/ /pubmed/28259932 http://dx.doi.org/10.3892/ijmm.2017.2902 Text en Copyright: © Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wu, Lin
Chen, Mingyu
Mao, Huijuan
Wang, Ningning
Zhang, Bo
Zhao, Xiufen
Qian, Jun
Xing, Changying
Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes
title Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes
title_full Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes
title_fullStr Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes
title_full_unstemmed Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes
title_short Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes
title_sort albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal fc receptor in glomerular podocytes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360426/
https://www.ncbi.nlm.nih.gov/pubmed/28259932
http://dx.doi.org/10.3892/ijmm.2017.2902
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