Overcoming multidrug resistance by co-delivery of Mdr-1 and survivin-targeting RNA with reduction-responsible cationic poly(beta-amino esters)

doi:10.1016/j.biomaterials.2012.05.039

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	Overcoming multidrug resistance by co-delivery of Mdr-1 and survivin-targeting RNA with reduction-responsible cationic poly(beta-amino esters)
	Yin, Qi; Shen, Jianan; Chen, Lingli; Zhang, Zhiwen; Gu, Wangwen; Li, Yaping
刊名	BIOMATERIALS
	2012-09
卷号	33 期号:27 页码:6495-6506
关键词	Poly(beta-amino esters) RNA P-glycoprotein Survivin Multidrug resistance
ISSN号	0142-9612
DOI	10.1016/j.biomaterials.2012.05.039
文献子类	Article
英文摘要	Multidrug resistance (MDR) remains one of the main challenges in the successful chemotherapy of human cancer. RNA interference (RNAi) strategy aiming at only one cause of MDR was widely applied, nevertheless hardly obtained satisfactory tumor-suppressing effect. In this work, a new attempt to package two kinds of RNA with different functions into one vector and reverse MDR against two different mechanisms via RNAi was carried out. A new bioreducible poly (beta-amino esters) (PAEs), poly[bis(2-hydroxylethyl)-disulfide-diacrylate-beta-tetraethylenepentamine] (PAP) was synthesized by Michael addition reaction. The PAEs/RNA complex nanoparticles (PAEN) were prepared. The experimental results demonstrated that co-delivery of iMdr-1-shRNA and iSurvivin-shRNA could be achieved by a single vector, and interfering two genes simultaneously had a synergistic effect on overcoming MDR. PAEN lowered the IC50 value of doxorubicin (DOX) in MDR tumor cells to a comparable level to that in the sensitive cell line through down-regulating the expression of P-gp and Survivin, and decreased the tumor volumes in mice xenograft model bearing DOX-resistant human breast cancer when combined with DOX. These results illustrated that PAEN could be applied as potential efficient non-viral RNA carriers for reversing MDR. (c) 2012 Elsevier Ltd. All rights reserved.
资助项目	The National Basic Research Program of China[2010CB934000] ; The National Basic Research Program of China[2012CB932500] ; National Natural Science Foundation of China[30925041] ; National Natural Science Foundation of China[81102388] ; Shanghai Elitist Program[11XD1406200]
WOS关键词	DRUG-RESISTANCE ; GENE-EXPRESSION ; P-GP ; CANCER ; NANOPARTICLES ; CELLS ; DOXORUBICIN ; TRANSPORTERS ; INHIBITION ; VERAPAMIL
WOS研究方向	Engineering ; Materials Science
语种	英语
出版者	ELSEVIER SCI LTD
WOS记录号	WOS:000307148200020
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277979]
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 Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yin, Qi,Shen, Jianan,Chen, Lingli,et al. Overcoming multidrug resistance by co-delivery of Mdr-1 and survivin-targeting RNA with reduction-responsible cationic poly(beta-amino esters)[J]. BIOMATERIALS,2012,33(27):6495-6506.
APA	Yin, Qi,Shen, Jianan,Chen, Lingli,Zhang, Zhiwen,Gu, Wangwen,&Li, Yaping.(2012).Overcoming multidrug resistance by co-delivery of Mdr-1 and survivin-targeting RNA with reduction-responsible cationic poly(beta-amino esters).BIOMATERIALS,33(27),6495-6506.
MLA	Yin, Qi,et al."Overcoming multidrug resistance by co-delivery of Mdr-1 and survivin-targeting RNA with reduction-responsible cationic poly(beta-amino esters)".BIOMATERIALS 33.27(2012):6495-6506.