Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

Yumin Zhang,1,* Junhui Zhou,2,* Cuihong Yang,1 Weiwei Wang,3 Liping Chu,1 Fan Huang,1 Qiang Liu,1 Liandong Deng,2 Deling Kong,3 Jianfeng Liu,1 Jinjian Liu1 1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Scien...

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Autores principales:	Zhang Y, Zhou J, Yang C, Wang W, Chu L, Huang F, Liu Q, Deng L, Kong D, Liu J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	core cross-linking folic acid targeting self-assembling curcumin drug delivery micelles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9804716b7cdb40d3a5c6fcf37aa77dd5
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spelling	oai:doaj.org-article:9804716b7cdb40d3a5c6fcf37aa77dd52021-12-02T03:58:32ZFolic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors1178-2013https://doaj.org/article/9804716b7cdb40d3a5c6fcf37aa77dd52016-03-01T00:00:00Zhttps://www.dovepress.com/folic-acid-targeted-disulfide-based-cross-linking-micelle-for-enhanced-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yumin Zhang,1,* Junhui Zhou,2,* Cuihong Yang,1 Weiwei Wang,3 Liping Chu,1 Fan Huang,1 Qiang Liu,1 Liandong Deng,2 Deling Kong,3 Jianfeng Liu,1 Jinjian Liu1 1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, 2Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, 3Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People’s Republic of China *These authors contributed equally in this work Abstract: Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. Keywords: core cross-linking, folic acid targeting, self-assembling, curcumin, drug delivery, micellesZhang YZhou JYang CWang WChu LHuang FLiu QDeng LKong DLiu JLiu JDove Medical Pressarticlecore cross-linkingfolic acid targetingself-assemblingcurcumindrug deliverymicellesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1119-1130 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	core cross-linking folic acid targeting self-assembling curcumin drug delivery micelles Medicine (General) R5-920
spellingShingle	core cross-linking folic acid targeting self-assembling curcumin drug delivery micelles Medicine (General) R5-920 Zhang Y Zhou J Yang C Wang W Chu L Huang F Liu Q Deng L Kong D Liu J Liu J Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors
description	Yumin Zhang,1,* Junhui Zhou,2,* Cuihong Yang,1 Weiwei Wang,3 Liping Chu,1 Fan Huang,1 Qiang Liu,1 Liandong Deng,2 Deling Kong,3 Jianfeng Liu,1 Jinjian Liu1 1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, 2Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, 3Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People’s Republic of China *These authors contributed equally in this work Abstract: Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. Keywords: core cross-linking, folic acid targeting, self-assembling, curcumin, drug delivery, micelles
format	article
author	Zhang Y Zhou J Yang C Wang W Chu L Huang F Liu Q Deng L Kong D Liu J Liu J
author_facet	Zhang Y Zhou J Yang C Wang W Chu L Huang F Liu Q Deng L Kong D Liu J Liu J
author_sort	Zhang Y
title	Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors
title_short	Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors
title_full	Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors
title_fullStr	Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors
title_full_unstemmed	Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors
title_sort	folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/9804716b7cdb40d3a5c6fcf37aa77dd5
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Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

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