Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy
文献类型：期刊论文
| 作者 | Zhang, Pengcheng1 ; Hu, Luojuan2; Yin, Qi1; Feng, Linyin2; Li, Yaping1
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| 刊名 | MOLECULAR PHARMACEUTICS
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| 出版日期 | 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. |
| WOS关键词 | IN-VITRO ; INTEGRINS ; TAXOL ; GLIOBLASTOMA ; ENDOCYTOSIS ; EXPRESSION ; TRANSPORT ; DELIVERY ; PRODRUGS ; DENSITY |
| 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研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000304728700006 |
| 出版者 | AMER CHEMICAL SOC |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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