Co-delivery of doxorubicin and RNA using pH-sensitive poly (beta-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer

doi:10.1016/j.biomaterials.2014.04.025

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	Co-delivery of doxorubicin and RNA using pH-sensitive poly (beta-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer
	Tang, Shan; Yin, Qi; Zhang, Zhiwen; Gu, Wangwen; Chen, Lingli; Yu, Haijun; Huang, Yongzhuo; Chen, Xianzhi; Xu, Minghua; Li, Yaping
刊名	BIOMATERIALS
	2014-07
卷号	35 期号:23 页码:6047-6059
关键词	Co-delivery Doxorubicin Multidrug resistance PH-sensitive Poly (beta-amino ester) RNA interference
ISSN号	0142-9612
DOI	10.1016/j.biomaterials.2014.04.025
文献子类	Article
英文摘要	An appropriate co-delivery system for chemotherapeutic agents and nucleic acid drugs will provide a more efficacious approach for the treatment of breast cancer by reversing multidrug resistance (MDR). In this work, a new amphiphilic poly (beta-amino ester), poly[(1,4-butanediol)-diacrylate-beta-5-polyethylenimine]-block-poly[(1,4-butanediol)-diacrylate-beta-5-hydroxy amylamine] (PDP-PDHA) was synthesized, and the doxorubicin (DOX) and survivin-targeting shRNA (shSur) co-loading nanoparticle (PDNs) were prepared. The pH-sensitive poly[(1,4-butanediol) diacrylate-beta-5-hydroxy amylamine] (PDHA) endowed PDNs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the cytotoxicity of DOX and the transfection efficiency. PDNs also increased the DOX accumulation, down-regulated 57.7% survivin expression, induced 80.8% cell apoptosis and changed the cell cycle in MCF-7/ADR cells. In the MCF-7/ADR tumor-bearing mice models, after administrated intravenously, PDNs raised the accumulation of DOX and shSur in the tumor tissue by 10.4 and 20.2 folds, respectively, resulting in obvious inhibition of the tumor growth with tumor inhibiting rate of 95.9%. The combination of DOX and RNA interference showed synergistic effect on overcoming MDR. Therefore, PDNs could be a promising co-delivery vector for effective therapy of drug resistant breast cancer. (C) 2014 Elsevier Ltd. All rights reserved.
资助项目	National Basic Research Program of China[2010CB934000] ; National Basic Research Program of China[2013CB932503] ; National Basic Research Program of China[2014CB931902] ; National Natural Science Foundation of China[81230029] ; National Natural Science Foundation of China[81302712] ; Shanghai Program[11nm0505900]
WOS关键词	GENE DELIVERY ; INTRACELLULAR TRAFFICKING ; INTERFERING RNAS ; DRUG-RESISTANCE ; FLIP-FLOP ; THERAPY ; CELLS ; NANOCARRIERS ; TRANSFECTION ; EXPRESSION
WOS研究方向	Engineering ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000337212200007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277016]
专题	药物制剂研究中心
通讯作者	Li, Yaping
作者单位	Chinese Acad Sci, Shanghai Inst Mat Medico, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Tang, Shan,Yin, Qi,Zhang, Zhiwen,et al. Co-delivery of doxorubicin and RNA using pH-sensitive poly (beta-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer[J]. BIOMATERIALS,2014,35(23):6047-6059.
APA	Tang, Shan.,Yin, Qi.,Zhang, Zhiwen.,Gu, Wangwen.,Chen, Lingli.,...&Li, Yaping.(2014).Co-delivery of doxorubicin and RNA using pH-sensitive poly (beta-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer.BIOMATERIALS,35(23),6047-6059.
MLA	Tang, Shan,et al."Co-delivery of doxorubicin and RNA using pH-sensitive poly (beta-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer".BIOMATERIALS 35.23(2014):6047-6059.