PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications

Guangtao Xu,1,2 Huan Gu,1,3 Bo Hu,4 Fei Tong,2 Daojun Liu,1 Xiaojun Yu,1 Yongxia Zheng,1,2 Jiang Gu1 1Department of Pathology and Chemistry, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Molecular Diagnosis and Personalized Medicine, Shanto...

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Autores principales:	Xu G, Gu H, Hu B, Tong F, Liu D, Yu X, Zheng Y, Gu J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	PEG-b-(PELG-g-PLL) TNF-α ischemia-reperfusion brain Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/85cc48743c4244fe9add7790ec5ae308
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spelling	oai:doaj.org-article:85cc48743c4244fe9add7790ec5ae3082021-12-02T00:46:39ZPEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications1178-2013https://doaj.org/article/85cc48743c4244fe9add7790ec5ae3082017-03-01T00:00:00Zhttps://www.dovepress.com/peg-b-pelg-g-pll-nanoparticles-as-tnf-alpha-nanocarriers-potential-cer-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Guangtao Xu,1,2 Huan Gu,1,3 Bo Hu,4 Fei Tong,2 Daojun Liu,1 Xiaojun Yu,1 Yongxia Zheng,1,2 Jiang Gu1 1Department of Pathology and Chemistry, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Molecular Diagnosis and Personalized Medicine, Shantou University Medical College, Shantou, Guangdong, 2Department of Pathology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang, People’s Republic of China; 3Department of Physics, University of Maryland, College Park, Annapolis, MD, USA; 4Department of Chemical Pathology, Jiaxing Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, People’s Republic of China Abstract: Brain ischemia/reperfusion (I/R) injury (BI/RI) is a leading cause of death and disability worldwide. However, the outcome of pharmacotherapy for BI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering neuronal activity in BI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of tumor necrosis factor (TNF)-α-loaded poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (TNF-α/PEG-b-(PELG-g-PLL)) nanoparticles on BI/RI. The particle size of PEG-b-(PELG-g-PLL) and the loading and release rates of TNF-α were determined. The nanoparticle cytotoxicity was evaluated in vitro using rat cortical neurons. Sprague Dawley rats were preconditioned with free TNF-α or TNF-α/PEG-b-(PELG-g-PLL) polyplexes and then subjected to 2 hours ischemia and 22 hours reperfusion. Brain edema was assessed using the brain edema ratio, and the antioxidative activity was assessed by measuring the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content in the brain tissue. We further estimated the inflammatory activity and apoptosis level by determining the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-10, and nitric oxide (NO), as well as the expression of glial fibrillary acidic protein (GFAP), intercellular adhesion molecule-1 (ICAM-1), and cysteine aspartase-3 (caspase-3), in the brain tissue. We provide evidence that TNF-α preconditioning attenuated the oxidative stress injury, the inflammatory activity, and the apoptosis level in I/R-induced cerebral injury, while the application of block copolymer PEG-b-(PELG-g-PLL) as a potential TNF-α nanocarrier with sustained release significantly enhanced the bioavailability of TNF-α. We propose that the block copolymer PEG-b-(PELG-g-PLL) may function as a potent nanocarrier for augmenting BI/RI pharmacotherapy, with unprecedented clinical benefits. Further studies are needed to better clarify the underlying mechanisms. Keywords: PEG-b-(PELG-g-PLL), TNF-α, ischemia/reperfusion, brainXu GGu HHu BTong FLiu DYu XZheng YGu JDove Medical PressarticlePEG-b-(PELG-g-PLL)TNF-αischemia-reperfusionbrainMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2243-2254 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	PEG-b-(PELG-g-PLL) TNF-α ischemia-reperfusion brain Medicine (General) R5-920
spellingShingle	PEG-b-(PELG-g-PLL) TNF-α ischemia-reperfusion brain Medicine (General) R5-920 Xu G Gu H Hu B Tong F Liu D Yu X Zheng Y Gu J PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications
description	Guangtao Xu,1,2 Huan Gu,1,3 Bo Hu,4 Fei Tong,2 Daojun Liu,1 Xiaojun Yu,1 Yongxia Zheng,1,2 Jiang Gu1 1Department of Pathology and Chemistry, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Molecular Diagnosis and Personalized Medicine, Shantou University Medical College, Shantou, Guangdong, 2Department of Pathology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang, People’s Republic of China; 3Department of Physics, University of Maryland, College Park, Annapolis, MD, USA; 4Department of Chemical Pathology, Jiaxing Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Jiaxing, Zhejiang, People’s Republic of China Abstract: Brain ischemia/reperfusion (I/R) injury (BI/RI) is a leading cause of death and disability worldwide. However, the outcome of pharmacotherapy for BI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering neuronal activity in BI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of tumor necrosis factor (TNF)-α-loaded poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (TNF-α/PEG-b-(PELG-g-PLL)) nanoparticles on BI/RI. The particle size of PEG-b-(PELG-g-PLL) and the loading and release rates of TNF-α were determined. The nanoparticle cytotoxicity was evaluated in vitro using rat cortical neurons. Sprague Dawley rats were preconditioned with free TNF-α or TNF-α/PEG-b-(PELG-g-PLL) polyplexes and then subjected to 2 hours ischemia and 22 hours reperfusion. Brain edema was assessed using the brain edema ratio, and the antioxidative activity was assessed by measuring the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content in the brain tissue. We further estimated the inflammatory activity and apoptosis level by determining the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-10, and nitric oxide (NO), as well as the expression of glial fibrillary acidic protein (GFAP), intercellular adhesion molecule-1 (ICAM-1), and cysteine aspartase-3 (caspase-3), in the brain tissue. We provide evidence that TNF-α preconditioning attenuated the oxidative stress injury, the inflammatory activity, and the apoptosis level in I/R-induced cerebral injury, while the application of block copolymer PEG-b-(PELG-g-PLL) as a potential TNF-α nanocarrier with sustained release significantly enhanced the bioavailability of TNF-α. We propose that the block copolymer PEG-b-(PELG-g-PLL) may function as a potent nanocarrier for augmenting BI/RI pharmacotherapy, with unprecedented clinical benefits. Further studies are needed to better clarify the underlying mechanisms. Keywords: PEG-b-(PELG-g-PLL), TNF-α, ischemia/reperfusion, brain
format	article
author	Xu G Gu H Hu B Tong F Liu D Yu X Zheng Y Gu J
author_facet	Xu G Gu H Hu B Tong F Liu D Yu X Zheng Y Gu J
author_sort	Xu G
title	PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications
title_short	PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications
title_full	PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications
title_fullStr	PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications
title_full_unstemmed	PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications
title_sort	peg-b-(pelg-g-pll) nanoparticles as tnf-α nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/85cc48743c4244fe9add7790ec5ae308
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PEG-b-(PELG-g-PLL) nanoparticles as TNF-&alpha; nanocarriers: potential cerebral ischemia/reperfusion injury therapeutic applications

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