iRGD Conjugated TPGS Mediates Codelivery of Paclitaxel and Survivin shRNA for the Reversal of Lung Cancer Resistance

doi:10.1021/mp400576f

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	iRGD Conjugated TPGS Mediates Codelivery of Paclitaxel and Survivin shRNA for the Reversal of Lung Cancer Resistance
	Shen, Jianan 1; Meng, Qingshuo 1; Sui, Huiping 1,2; Yin, Qi1 ; Zhang, Zhiwen1 ; Yu, Haijun1 ; Li, Yaping1
刊名	MOLECULAR PHARMACEUTICS
	2014-08
卷号	11 期号:8 页码:2579-2591
关键词	paclitaxel survivin shRNA TPGS lung cancer nanoparticles
ISSN号	1543-8384
DOI	10.1021/mp400576f
文献子类	Article
英文摘要	Multidrug resistance (MDR) is one of the major obstacles in tumor treatment. Herein, we reported an active targeting strategy with peptide-mediated nanoparticles deep into tumor parenchyma, which iRGD conjugated D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) mediated codelivery of paclitaxel (PTX) and survivin shRNA (shSur) for the reversal of lung cancer resistance. Pluronic P85-polyethyleneimine/TPGS complex nanoparticles incorporated with iRGD-TPGS conjugate codelivering PTX and shSur systems (iPTPNs) could induce effective cellular uptake, RNAi effects, and cytotoxicity on A549 and A549/T cells. In particular, iPTPNs showed superiority in biodistribution, survivin expression, tumor apoptosis, and antitumor efficacy by simultaneously exerting an enhanced permeability and retention (EPR) effect and iRGD mediated active targeting effects. iPTPNs significantly enhanced the accumulation of PTX and shSur, down-regulated survivin expression, and induced cell apoptosis in tumor tissue. The in vivo antitumor efficacy showed the tumor volume of iPTPNs group (10 mg/kg) was only 12.7% of the Taxol group. Therefore, the iRGD mediated PTX and shSur codelivery system could be a very powerful approach for the reversal and therapy of lung cancer resistance.
资助项目	National Basic Research Program of China[2010CB934000] ; National Basic Research Program of China[2013CB932704] ; National Basic Research Program of China[2013CB932503] ; National Natural Science Foundation of China[81230029] ; National Natural Science Foundation of China[81102388] ; Shanghai Program[11 nm0505900]
WOS关键词	DRUG-DELIVERY SYSTEMS ; IN-VIVO EVALUATION ; CELL-DEATH ; MULTIDRUG-RESISTANCE ; BLOOD COMPONENTS ; GENE DELIVERY ; CO-DELIVERY ; NANOPARTICLES ; ANGIOGENESIS ; INTEGRINS
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000339982900008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276967]
专题	药物制剂研究中心
通讯作者	Li, Yaping
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China
推荐引用方式 GB/T 7714	Shen, Jianan,Meng, Qingshuo,Sui, Huiping,et al. iRGD Conjugated TPGS Mediates Codelivery of Paclitaxel and Survivin shRNA for the Reversal of Lung Cancer Resistance[J]. MOLECULAR PHARMACEUTICS,2014,11(8):2579-2591.
APA	Shen, Jianan.,Meng, Qingshuo.,Sui, Huiping.,Yin, Qi.,Zhang, Zhiwen.,...&Li, Yaping.(2014).iRGD Conjugated TPGS Mediates Codelivery of Paclitaxel and Survivin shRNA for the Reversal of Lung Cancer Resistance.MOLECULAR PHARMACEUTICS,11(8),2579-2591.
MLA	Shen, Jianan,et al."iRGD Conjugated TPGS Mediates Codelivery of Paclitaxel and Survivin shRNA for the Reversal of Lung Cancer Resistance".MOLECULAR PHARMACEUTICS 11.8(2014):2579-2591.