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Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxorubicin
Jiang, Juan; Yang, Shi-jin; Wang, Jian-cheng; Yang, Li-juan; Xu, Zhen-zhong; Yang, Ting; Liu, Xiao-yan; Zhang, Qiang
关键词Drug-resistant tumor siRNA Doxorubicin RGD-modified liposome Targeting Sequential treatment
刊名EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
2010-10-01
DOI10.1016/j.ejpb.2010.06.011
76期:2页:170-178
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]SMALL INTERFERING RNAS ; IN-VIVO ; MULTIDRUG-RESISTANCE ; INTRACELLULAR DELIVERY ; SELECTIVE DELIVERY ; ENDOTHELIAL-CELLS ; TARGETED DELIVERY ; P-GLYCOPROTEIN ; GENE DELIVERY ; GROWTH-FACTOR
英文摘要

Tumor targeting drug delivery systems are being the ideal carriers of systemic administration for tumor therapy. We have reported previously that RGD peptide (arginine-glycine-aspartic acid)-modified liposomes containing drugs could increase targeting to tumor by binding with the integrin receptors overexpressed on tumor cells. RNA interference plays an important role on down-regulation of P-glycoprotein (P-gp), which is a drug efflux transporter overexpressed on multi-drug-resistant (MDR) tumor cells. To improve MDR tumor therapy, sequential treatment strategy with RGD-modified liposomes containing P-gp targeted small interference (siRNA) or doxorubicin (DOX) was reported in this study. When targeted via RGD to tumor-cell-surface and tumor neovasculature endothelial cell receptors, cationic liposomes could specifically deliver siRNAs to tumor cells and thus reverse drug resistance by down-regulation of P-gp, following administration of targeted liposomes containing DOX that inhibit formerly drug-resistant tumors. From the current results, the combination use of DOX and P-gp targeted siRNA showed significantly higher in vitro cytotoxicity in tumor cells than liposomal DOX alone. In vivo studies in a mouse model of drug-resistant MCF7/A tumor demonstrated significantly greater inhibition of tumor growth followed by the sequential treatment of RGD-modified liposomes containing siRNA or DOX when compared to liposomal DOX alone. Also, ex vivo tissue imaging studies have shown the accumulation of siRNA and DOX in tumors at same site-specific manner. These results suggested that the sequential treatment of P-gp gene silencing and cytotoxic drug with RGD-modified liposome drug delivery system could be a promising clinical treatment for drug-resistant tumors. (C) 2010 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000283756700003
项目编号30701056 ; 7083112 ; 20070001813 ; 2007CB935800 ; 2009CB930300
资助机构National Natural Science Foundation of China ; Beijing Natural Science Foundation of China ; Doctoral Foundation of Ministry of Education of China ; National Basic Research Program of China (973 Program)
引用统计
被引频次:102[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63020
专题北京大学药学院
北京大学药学院_药剂学系
北京大学第三临床医学院_呼吸科
北京大学口腔医学院_外科
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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Jiang, Juan,Yang, Shi-jin,Wang, Jian-cheng,et al. Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxorubicin[J]. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS,2010,76(2):170-178.
APA Jiang, Juan.,Yang, Shi-jin.,Wang, Jian-cheng.,Yang, Li-juan.,Xu, Zhen-zhong.,...&Zhang, Qiang.(2010).Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxorubicin.EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS,76(2),170-178.
MLA Jiang, Juan,et al."Sequential treatment of drug-resistant tumors with RGD-modified liposomes containing siRNA or doxorubicin".EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 76.2(2010):170-178.
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