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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doaj-1d5135687f664b5d8efc1bb2ad9c873c2020-11-24T20:59:45ZengDove Medical PressInternational Journal of Nanomedicine1176-91141178-20132013-11-012013Issue 142654276Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivoChen MGao XWang YChen HHe BLi YHan JZhang ZMingrong 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-fluorouracilhttp://www.dovepress.com/synthesis-of-liver-targeting-dual-ligand-modified-gcga5-fu-nanoparticl-a14914 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chen M Gao X Wang Y Chen H He B Li Y Han J Zhang Z |
spellingShingle |
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 International Journal of Nanomedicine |
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 |
series |
International Journal of Nanomedicine |
issn |
1176-9114 1178-2013 |
publishDate |
2013-11-01 |
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 |
url |
http://www.dovepress.com/synthesis-of-liver-targeting-dual-ligand-modified-gcga5-fu-nanoparticl-a14914 |
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