GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy

Danrong Hu, Omar Mezghrani, Lei Zhang, Yi Chen, Xue Ke, Tianyuan Ci Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: Novel breast carcinoma dual-targeted redox-responsive nanoparticles (...

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Autores principales:	Hu DR, Mezghrani O, Zhang L, Chen Y, Ke X, Ci TY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	self-assembled nanoparticles redox-responsive dual-ligand targeting hyaluronic acid cancer therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c591e6594b364e67ab69877b516ecf2c
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spelling	oai:doaj.org-article:c591e6594b364e67ab69877b516ecf2c2021-12-02T00:09:56ZGE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy1178-2013https://doaj.org/article/c591e6594b364e67ab69877b516ecf2c2016-10-01T00:00:00Zhttps://www.dovepress.com/ge11-peptide-modified-and-reduction-responsive-hyaluronic-acid-based-n-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Danrong Hu, Omar Mezghrani, Lei Zhang, Yi Chen, Xue Ke, Tianyuan Ci Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cholesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11–HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11–HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle’s structure and accelerating the drug release dramatically in the presence of intracellular reductive environment. Furthermore, the cellular uptake assay confirmed GE11–HA-ss-Chol NPs were taken up by MDA-MB-231 cells through CD44- and epidermal growth factor receptor-mediated endocytosis. The internalization pathways of GE11–HA-ss-Chol NPs might involve clathrin-mediated endocytosis and macropinocytosis. The intracellular distribution of DOX in GE11–HA-ss-Chol NPs showed a faster release and more efficient nuclear delivery than the insensitive control. Enhanced in vitro cytotoxicity of GE11–HA-ss-Chol DOX-NPs further confirmed the superiority of their dual-targeting and redox-responsive capacity. Moreover, in vivo imaging investigation in MDA-MB-231 tumor-bearing mice confirmed that GE11–HA-ss-Chol NPs labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide, a near-infrared fluorescence dye, possessed a preferable tumor accumulation ability as compared to the single-targeting counterpart (HA-ss-Chol NPs). The antitumor efficacy showed an improved therapy efficacy and lower systemic side effect. These results suggest GE11–HA-ss-Chol NPs provide a good potential platform for antitumor drugs. Keywords: self-assembled nanoparticles, redox responsive, dual-ligand targeting, hyaluronic acid, cancer therapyHu DRMezghrani OZhang LChen YKe XCi TYDove Medical Pressarticleself-assembled nanoparticlesredox-responsivedual-ligand targetinghyaluronic acidcancer therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 5125-5147 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	self-assembled nanoparticles redox-responsive dual-ligand targeting hyaluronic acid cancer therapy Medicine (General) R5-920
spellingShingle	self-assembled nanoparticles redox-responsive dual-ligand targeting hyaluronic acid cancer therapy Medicine (General) R5-920 Hu DR Mezghrani O Zhang L Chen Y Ke X Ci TY GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy
description	Danrong Hu, Omar Mezghrani, Lei Zhang, Yi Chen, Xue Ke, Tianyuan Ci Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cholesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11–HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11–HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle’s structure and accelerating the drug release dramatically in the presence of intracellular reductive environment. Furthermore, the cellular uptake assay confirmed GE11–HA-ss-Chol NPs were taken up by MDA-MB-231 cells through CD44- and epidermal growth factor receptor-mediated endocytosis. The internalization pathways of GE11–HA-ss-Chol NPs might involve clathrin-mediated endocytosis and macropinocytosis. The intracellular distribution of DOX in GE11–HA-ss-Chol NPs showed a faster release and more efficient nuclear delivery than the insensitive control. Enhanced in vitro cytotoxicity of GE11–HA-ss-Chol DOX-NPs further confirmed the superiority of their dual-targeting and redox-responsive capacity. Moreover, in vivo imaging investigation in MDA-MB-231 tumor-bearing mice confirmed that GE11–HA-ss-Chol NPs labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide, a near-infrared fluorescence dye, possessed a preferable tumor accumulation ability as compared to the single-targeting counterpart (HA-ss-Chol NPs). The antitumor efficacy showed an improved therapy efficacy and lower systemic side effect. These results suggest GE11–HA-ss-Chol NPs provide a good potential platform for antitumor drugs. Keywords: self-assembled nanoparticles, redox responsive, dual-ligand targeting, hyaluronic acid, cancer therapy
format	article
author	Hu DR Mezghrani O Zhang L Chen Y Ke X Ci TY
author_facet	Hu DR Mezghrani O Zhang L Chen Y Ke X Ci TY
author_sort	Hu DR
title	GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy
title_short	GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy
title_full	GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy
title_fullStr	GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy
title_full_unstemmed	GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy
title_sort	ge11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/c591e6594b364e67ab69877b516ecf2c
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_version_	1718403953219076096

GE11 peptide modified and reduction-responsive hyaluronic acid-based nanoparticles induced higher efficacy of doxorubicin for breast carcinoma therapy

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