Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy

doi:10.1021/mp200600t

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy
	Zhang, Pengcheng1 ; Hu, Luojuan 2; Yin, Qi1 ; Feng, Linyin2 ; Li, Yaping1
刊名	MOLECULAR PHARMACEUTICS
	2012-06
卷号	9 期号:6 页码:1590-1598
关键词	glioma blood-brain barrier micelle sequential targeting
ISSN号	1543-8384
DOI	10.1021/mp200600t
文献子类	Article
英文摘要	The effective chemotherapy for glioblastoma multiform (GBM) requires a nanomedicine that can both penetrate the blood-brain barrier (BBB) and target the glioma cells subsequently. In this study, Transferrin (Tf)modified cyclo-[Arg-Gly-Asp-o-Phe-Lys] (c[RGDfK])-paclitaxel conjugate (RP) loaded micelle (TRPM) was prepared and evaluated for its targeting efficiency, antiglioma activity, and toxicity in vitro and in vivo. Tf modification significantly enhanced the cellular uptake of TRPM by primary brain microvascular endothelial cells (BMEC) to 2.4-fold of RP loaded micelle (RPM) through Tf receptor mediated endocytosis, resulting in a high drug accumulation in the brain after intravenous injection.The c[RGDfK] modified paclitaxel (PTX) was released from micelle subsequently and targeted to integrin overexpressed glioma cells in vitro, and showed significantly prolonged retention in glioma tumor and peritumoral tissue. Most importantly, TRPM exhibited the strongest antiglioma activity, as the mean survival time of mice bearing intracranial U-87 MG glioma treated with TRPM (42.8 days) was significantly longer than those treated with Tf modified PTX loaded micelle (TPM) (39.5 days), PTX loaded micelle (PM) (34.8 days), Taxol (33.6 days), and saline (34.5 days). Noteworthy, TRPM did not lead to body weight loss compared with saline and was less toxic than TPM. These results indicated that TRPM could be a promising nanomedicine for glioma chemotherapy.
资助项目	The National Basic Research Program of China[2010CB934000] ; The National Basic Research Program of China[2007CB935804] ; National Natural Science Foundation of China[30925041] ; National Natural Science Foundation of China[30901866] ; Shanghai Elitist Program[11XD1406200]
WOS关键词	IN-VITRO ; INTEGRINS ; TAXOL ; GLIOBLASTOMA ; ENDOCYTOSIS ; EXPRESSION ; TRANSPORT ; DELIVERY ; PRODRUGS ; DENSITY
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:000304728700006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278061]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室药物制剂研究中心
通讯作者	Li, Yaping
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharm, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Pengcheng,Hu, Luojuan,Yin, Qi,et al. Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy[J]. MOLECULAR PHARMACEUTICS,2012,9(6):1590-1598.
APA	Zhang, Pengcheng,Hu, Luojuan,Yin, Qi,Feng, Linyin,&Li, Yaping.(2012).Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy.MOLECULAR PHARMACEUTICS,9(6),1590-1598.
MLA	Zhang, Pengcheng,et al."Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy".MOLECULAR PHARMACEUTICS 9.6(2012):1590-1598.