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: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2013
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| Acceso en línea: | https://doaj.org/article/1d5135687f664b5d8efc1bb2ad9c873c |
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| Sumario: | 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 |
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