Co-delivery of Cell-permeable Chimeric Apoptosis AVPIR(8) Peptide/p53 DNA for Cocktail Therapy

doi:10.1002/adfm.201300793

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	Co-delivery of Cell-permeable Chimeric Apoptosis AVPIR(8) Peptide/p53 DNA for Cocktail Therapy
	Wang, Huiyuan1 ; Guo, Qianqian 1; Jiang, Yifan 1; Liu, Ergang 1; Zhao, Yongxing 2; Wang, Huixin 2; Li, Yaping1 ; Huang, Yongzhuo1,3,4
刊名	ADVANCED FUNCTIONAL MATERIALS
	2013-12-23
卷号	23 期号:48 页码:6068-6075
关键词	apoptotic peptides cell-penetrating peptides p53 gene cocktail therapies doxorubicin
ISSN号	1616-301X
DOI	10.1002/adfm.201300793
文献子类	Article
英文摘要	The tetra-peptide AVPI, derived from the Smac/DIABLO N-terminal epitope, is able to trigger caspase activation and apoptotic process. However, its clinical value is greatly hampered by the nature of membrane-impermeability. Herein, the cell-penetrating chimeric apoptotic peptide of AVPIR(8) is synthesized, of which the apoptosis-induced AVPI is strategically blended with the cell-penetrating sequence of octaarginine (R-8). The dual-functionalized AVPIR(8) is not only potent in inducing apoptosis in tumor cells due to the cell penetration ability, but also is able to work as gene carrier for transfering the tumor suppressor p53 DNA into cells, thus constructing a co-delivery drug system (AVPIR(8)/p53). Such system efficiently promotes apoptosis in cancer cells while sparing normal cells, and its antitumor activity is further significantly enhanced in combination with doxorubicin as cocktail therapy. More importantly, the anticancer efficacy of the cocktail is demonstrated to be able to arrest tumor growth in two animal tumor models (melanoma and cervical cancers), respectively. The chemotherapeutic dose in the AVPIR(8)/p53-based cocktail is significantly reduced by 80%, compared to the monotherapy of doxorubicin. The present results show the promise of the co-delivered AVPIR(8)/p53 as adjuvant therapy for boosting the conventional chemotherapeutics, with a unique benefit of enhanced productive treatment outcomes yet greatly reduced adverse toxicity.
资助项目	National Basic Research Program of China[973 Program 2013CB932503] ; NSFC, China[91029743] ; NSFC, China[81172996] ; Shanghai Pu-jiang Scholar Program[11PJ1411800] ; Chinese Postdoctoral Science Foundation[2012M510097] ; Chinese Postdoctoral Science Foundation[2013T60478] ; School of Pharmacy, Fudan University & The Open Project Program of Key Lab of Smart Drug Delivery (Fudan University), MOE PLA, China[SDD2011-02]
WOS关键词	DRUG-INDUCED APOPTOSIS ; CANCER-CELLS ; BIR3 DOMAIN ; IN-VIVO ; SMAC/DIABLO ; SMAC ; CASPASES ; P53 ; INHIBITION ; ACTIVATION
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000328733800012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277329]
专题	药物制剂研究中心
通讯作者	Wang, Huixin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China; 3.Fudan Univ, MOE, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China; 4.PLA, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Huiyuan,Guo, Qianqian,Jiang, Yifan,et al. Co-delivery of Cell-permeable Chimeric Apoptosis AVPIR(8) Peptide/p53 DNA for Cocktail Therapy[J]. ADVANCED FUNCTIONAL MATERIALS,2013,23(48):6068-6075.
APA	Wang, Huiyuan.,Guo, Qianqian.,Jiang, Yifan.,Liu, Ergang.,Zhao, Yongxing.,...&Huang, Yongzhuo.(2013).Co-delivery of Cell-permeable Chimeric Apoptosis AVPIR(8) Peptide/p53 DNA for Cocktail Therapy.ADVANCED FUNCTIONAL MATERIALS,23(48),6068-6075.
MLA	Wang, Huiyuan,et al."Co-delivery of Cell-permeable Chimeric Apoptosis AVPIR(8) Peptide/p53 DNA for Cocktail Therapy".ADVANCED FUNCTIONAL MATERIALS 23.48(2013):6068-6075.