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	A specific drug targeting system based on polyhydroxyalkanoate granule binding protein PhaP fused with targeted cell ligands
	Yao, Yong-Chao ; Zhan, Xiao-Yong ; Zhang, Jing ; Zou, Xiang-Hui ; Wang, Zhi-Hui ; Xiong, Yu-Cui ; Chen, Jiong ; Chen, Guo-Qiang
	2010-05-11 ; 2010-05-11
关键词	PHB Polyhydroxyalkanoates Drug delivery Granule binding protein PhaP Receptor-mediated-endocytosis EPIDERMAL-GROWTH-FACTOR RECEPTOR-MEDIATED ENDOCYTOSIS RALSTONIA-EUTROPHA H16 IN-VIVO DELIVERY-SYSTEMS ANTIBIOTIC RELEASE CARCINOMA-CELLS GENE-TRANSFER DNA DELIVERY PLASMID DNA Engineering, Biomedical Materials Science, Biomaterials
中文摘要	Polyhydroxyalkanoates (PHA) is a family of intracellular biopolyesters produced by many bacteria. PHA granule binding protein PhaP is able to bind to hydrophobic polymers via strong hydrophobic interaction. A receptor-mediated drug delivery system was developed in this study based on PhaP. The system consists of PHA nanoparticles, PhaP and polypeptide or protein ligands fused to PhaP. The PHA nanciparticles were used to package mostly hydrophobic drugs; PhaP fused with ligands produced by over-expression of their corresponding genes in Pichia pastoris, or E. colt was able to attach to hydrophobic PHA nanoparticle. At the end, the ligands were able to pull the PhaP-PHA nanoparticles to the targeted cells with receptors recognized by the ligands. It was found in this study that the receptor-mediated drug specific delivery system ligand-PhaP-PHA nanoparticles were taken up by macrophages, hepatocellular carcinoma cell BEL7402 in vitro and liver, hepatocellular carcinoma cells in vivo, respectively, when the ligands were mannosylated human alpha 1-acid glycoprotein (hAGP) and human epidermal growth factor (hEGF), respectively, which were able to bind to receptors of macrophages or hepatocellular carcinoma cells. The nanoparticle system was clearly visible in the targeted cells and organs (liver or tumor) under fluorescence microscopy when rhodamine B isothiocyanate (RBITC) was used as a delivery model drug due to the specific targeting effect created by specific ligand and receptor binding. The delivery system of hEGF-PhaP-nanoparticles carrying RBITC was found to be endocytosed by the tumor cells in tumorous model mice. Thus, the ligand-PhaP-PHA specific drug delivery system was proven effective both in vitro and in vivo. (c) 2008 Elsevier Ltd. All rights reserved.
语种	英语 ; 英语
出版者	ELSEVIER SCI LTD ; OXFORD ; THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/26936]
专题	清华大学
推荐引用方式 GB/T 7714	Yao, Yong-Chao,Zhan, Xiao-Yong,Zhang, Jing,et al. A specific drug targeting system based on polyhydroxyalkanoate granule binding protein PhaP fused with targeted cell ligands[J],2010, 2010.
APA	Yao, Yong-Chao.,Zhan, Xiao-Yong.,Zhang, Jing.,Zou, Xiang-Hui.,Wang, Zhi-Hui.,...&Chen, Guo-Qiang.(2010).A specific drug targeting system based on polyhydroxyalkanoate granule binding protein PhaP fused with targeted cell ligands..
MLA	Yao, Yong-Chao,et al."A specific drug targeting system based on polyhydroxyalkanoate granule binding protein PhaP fused with targeted cell ligands".(2010).

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