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Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury

In an attempt to improve therapeutic efficacy of dexamethasone (DXM)-loaded solid lipid nanoparticles (NPs) for renal ischemia-reperfusion injury (IRI)-induced acute renal injury (AKI), sialic acid (SA) is used as a ligand to target the inflamed vascular endothelium. DXM-loaded SA-conjugated polyeth...

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Autores principales: Hu, Jing-Bo, Song, Gui-Ling, Liu, Di, Li, Shu-Juan, Wu, Jia-Hui, Kang, Xu-Qi, Qi, Jing, Jin, Fei-Yang, Wang, Xiao-Juan, Xu, Xiao-Ling, Ying, Xiao-Ying, Yu, Lian, You, Jian, Du, Yong-Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241018/
https://www.ncbi.nlm.nih.gov/pubmed/29188738
http://dx.doi.org/10.1080/10717544.2017.1410258
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author Hu, Jing-Bo
Song, Gui-Ling
Liu, Di
Li, Shu-Juan
Wu, Jia-Hui
Kang, Xu-Qi
Qi, Jing
Jin, Fei-Yang
Wang, Xiao-Juan
Xu, Xiao-Ling
Ying, Xiao-Ying
Yu, Lian
You, Jian
Du, Yong-Zhong
author_facet Hu, Jing-Bo
Song, Gui-Ling
Liu, Di
Li, Shu-Juan
Wu, Jia-Hui
Kang, Xu-Qi
Qi, Jing
Jin, Fei-Yang
Wang, Xiao-Juan
Xu, Xiao-Ling
Ying, Xiao-Ying
Yu, Lian
You, Jian
Du, Yong-Zhong
author_sort Hu, Jing-Bo
collection PubMed
description In an attempt to improve therapeutic efficacy of dexamethasone (DXM)-loaded solid lipid nanoparticles (NPs) for renal ischemia-reperfusion injury (IRI)-induced acute renal injury (AKI), sialic acid (SA) is used as a ligand to target the inflamed vascular endothelium. DXM-loaded SA-conjugated polyethylene glycol (PEG)ylated NPs (SA-NPs) are prepared via solvent diffusion method and show the good colloidal stability. SA-NPs reduce apoptotic human umbilical vein endothelial cells (HUVECs) via downregulating oxidative stress-induced Bax, upregulating Bcl-xL, and inhibiting Caspase-3 and Caspase-9 activation. Cellular uptake results suggest SA-NPs can be specifically internalized by the inflamed vascular endothelial cells (H(2)O(2)-pretreated HUVECs), and the mechanism is associated with the specific binding between SA and E-selectin receptor expressed on the inflamed vascular endothelial cells. Bio-distribution results further demonstrated the enhanced renal accumulation of DXM is achieved in AKI mice treated with SA-NPs, and its content is 2.70- and 5.88-fold higher than those treated with DXM and NPs at 6 h after intravenous administration, respectively. Pharmacodynamic studies demonstrate SA-NPs effectively ameliorate renal functions in AKI mice, as reflected by improved blood biochemical indexes, histopathological changes, oxidative stress levels and pro-inflammatory cytokines. Moreover, SA-NPs cause little negative effects on lymphocyte count and bone mineral density while DXM leads to severe osteoporosis. It is concluded that SA-NPs provide an efficient and targeted delivery of DXM for ischemia-reperfusion-induced injury-induced AKI, with improved therapeutic outcomes and reduced adverse effects.
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spelling pubmed-82410182021-07-08 Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury Hu, Jing-Bo Song, Gui-Ling Liu, Di Li, Shu-Juan Wu, Jia-Hui Kang, Xu-Qi Qi, Jing Jin, Fei-Yang Wang, Xiao-Juan Xu, Xiao-Ling Ying, Xiao-Ying Yu, Lian You, Jian Du, Yong-Zhong Drug Deliv Original Article In an attempt to improve therapeutic efficacy of dexamethasone (DXM)-loaded solid lipid nanoparticles (NPs) for renal ischemia-reperfusion injury (IRI)-induced acute renal injury (AKI), sialic acid (SA) is used as a ligand to target the inflamed vascular endothelium. DXM-loaded SA-conjugated polyethylene glycol (PEG)ylated NPs (SA-NPs) are prepared via solvent diffusion method and show the good colloidal stability. SA-NPs reduce apoptotic human umbilical vein endothelial cells (HUVECs) via downregulating oxidative stress-induced Bax, upregulating Bcl-xL, and inhibiting Caspase-3 and Caspase-9 activation. Cellular uptake results suggest SA-NPs can be specifically internalized by the inflamed vascular endothelial cells (H(2)O(2)-pretreated HUVECs), and the mechanism is associated with the specific binding between SA and E-selectin receptor expressed on the inflamed vascular endothelial cells. Bio-distribution results further demonstrated the enhanced renal accumulation of DXM is achieved in AKI mice treated with SA-NPs, and its content is 2.70- and 5.88-fold higher than those treated with DXM and NPs at 6 h after intravenous administration, respectively. Pharmacodynamic studies demonstrate SA-NPs effectively ameliorate renal functions in AKI mice, as reflected by improved blood biochemical indexes, histopathological changes, oxidative stress levels and pro-inflammatory cytokines. Moreover, SA-NPs cause little negative effects on lymphocyte count and bone mineral density while DXM leads to severe osteoporosis. It is concluded that SA-NPs provide an efficient and targeted delivery of DXM for ischemia-reperfusion-induced injury-induced AKI, with improved therapeutic outcomes and reduced adverse effects. Taylor & Francis 2017-11-30 /pmc/articles/PMC8241018/ /pubmed/29188738 http://dx.doi.org/10.1080/10717544.2017.1410258 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Hu, Jing-Bo
Song, Gui-Ling
Liu, Di
Li, Shu-Juan
Wu, Jia-Hui
Kang, Xu-Qi
Qi, Jing
Jin, Fei-Yang
Wang, Xiao-Juan
Xu, Xiao-Ling
Ying, Xiao-Ying
Yu, Lian
You, Jian
Du, Yong-Zhong
Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury
title Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury
title_full Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury
title_fullStr Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury
title_full_unstemmed Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury
title_short Sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury
title_sort sialic acid-modified solid lipid nanoparticles as vascular endothelium-targeting carriers for ischemia-reperfusion-induced acute renal injury
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241018/
https://www.ncbi.nlm.nih.gov/pubmed/29188738
http://dx.doi.org/10.1080/10717544.2017.1410258
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