Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo

Mingrong Cheng,1,2,* Xiaoyan Gao,3,* Yong Wang,4,* Houxiang Chen,5 Bing He,6 Yingchun Li,2 Jiang Han,1 Zhiping Zhang11Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Endoscopy, 3Department of Plastic Surgery, Pud...

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Autores principales: Chen M, Gao X, Wang Y, Chen H, He B, Li Y, Han J, Zhang Z
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Publicado: Dove Medical Press 2013
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spelling oai:doaj.org-article:1d5135687f664b5d8efc1bb2ad9c873c2021-12-02T07:14:16ZSynthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo1176-91141178-2013https://doaj.org/article/1d5135687f664b5d8efc1bb2ad9c873c2013-11-01T00:00:00Zhttp://www.dovepress.com/synthesis-of-liver-targeting-dual-ligand-modified-gcga5-fu-nanoparticl-a14914https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Mingrong Cheng,1,2,* Xiaoyan Gao,3,* Yong Wang,4,* Houxiang Chen,5 Bing He,6 Yingchun Li,2 Jiang Han,1 Zhiping Zhang11Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Endoscopy, 3Department of Plastic Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China; 4School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China; 5Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People’s Republic of China; 6Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People's Republic of China *These authors equally contributed to this research Abstract: Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival. Keywords: liver cancer, chemotherapy, targeted therapy, 5-fluorouracilChen MGao XWang YChen HHe BLi YHan JZhang ZDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss Issue 1, Pp 4265-4276 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Chen M
Gao X
Wang Y
Chen H
He B
Li Y
Han J
Zhang Z
Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo
description Mingrong Cheng,1,2,* Xiaoyan Gao,3,* Yong Wang,4,* Houxiang Chen,5 Bing He,6 Yingchun Li,2 Jiang Han,1 Zhiping Zhang11Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Endoscopy, 3Department of Plastic Surgery, Pudong New Area District Zhoupu Hospital, Shanghai, People's Republic of China; 4School of Materials Science and Engineering, Wuhan University of Technology, Wuhan, People’s Republic of China; 5Zhejiang Huafon Fiber Research Institute, Zhejiang Huafon Spandex Co, Ltd, Wenzhou, People’s Republic of China; 6Department of General Surgery, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People's Republic of China *These authors equally contributed to this research Abstract: Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival. Keywords: liver cancer, chemotherapy, targeted therapy, 5-fluorouracil
format article
author Chen M
Gao X
Wang Y
Chen H
He B
Li Y
Han J
Zhang Z
author_facet Chen M
Gao X
Wang Y
Chen H
He B
Li Y
Han J
Zhang Z
author_sort Chen M
title Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo
title_short Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo
title_full Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo
title_fullStr Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo
title_full_unstemmed Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo
title_sort synthesis of liver-targeting dual-ligand modified gcga/5-fu nanoparticles and their characteristics in vitro and in vivo
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/1d5135687f664b5d8efc1bb2ad9c873c
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