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Dual Receptor-Specific Peptides Modified Liposomes as VEGF siRNA Vector for Tumor-Targeting Therapy
Yang, Zhenzhen; Xiang, Bai; Dong, Dawen; Wang, Zhanzhang; Li, Jingquan; Qi, Xianrong
关键词Angiopep Anti-angiogenesis Dual-modified Liposomes Glioma Tlyp-1 Vegf Sirna
刊名CURRENT GENE THERAPY
2014
14期:4页:289-299
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Genetics & Heredity
研究领域[WOS]Genetics & Heredity
关键词[WOS]DENSITY-LIPOPROTEIN RECEPTOR ; ENDOTHELIAL GROWTH-FACTOR ; DRUG-DELIVERY SYSTEM ; CANCER-CELLS ; PROSTATE-CANCER ; INTERFERING RNA ; BRAIN ; NANOPARTICLES ; THERAPEUTICS ; PROTEIN
英文摘要

Tumor angiogenesis involves multiple signaling pathways that provide potential therapeutic targets to inhibit tumor growth and metastasis. Regarding the significant role of vascular endothelial growth factor (VEGF) in angiogenesis and tumor progression, VEGF sequence-specific small interfering RNA (siRNA) for anti-angiogenic tumor therapy are under development. In the present study, dual-modified liposomes (At-Lp) was designed by attaching two receptor-specific peptides, Angiopep and tLyP-1, which specifically targeting low-density lipoprotein receptor (LRP) for brain tumor targeting and neuropilin-1 receptor (NRP-1) for tumor penetration, respectively. Gene transfection and silencing, and antitumor effect of the At-Lp loaded with VEGF siRNA were evaluated in vitro and in orthotopic xenograft models of U87 MG tumor. The At-Lp significantly enhanced cellular uptake (2-fold) and down-regulated expression of VEGF in U87 MG glioblastoma cells compared with non-modified and single-modified liposomes. The internalization of the At-Lp into tumor cells was taken via the enhanced permeability and retention effect and receptor-mediated endocytosis, followed by an effective endosomal escape of loaded siRNA into the cytoplasm. The At-Lp showed great superiority in inhibition of tumor growth, anti-angiogenesis, expression of VEGF and apoptosis effect after in vivo application against nude mice bearing U87 MG glioblastoma without activation of system-associated toxicity and the innate immune response. These results demonstrated that the combination of two receptor-specific peptides-mediated liposomes presented a promising platform for effective targeting delivery of siRNA for cancer anti-angiogenic therapy.

语种英语
WOS记录号WOS:000341362700005
项目编号2013CB932501 ; 81273454 ; 7132113 ; 20100001110056 ; 20130001110055 ; BMU20110263
资助机构National Basic Research Program ; NSFC ; Beijing NSF ; Doctoral Foundation of the Ministry of Education ; Innovation Team of Ministry of Education
引用统计
被引频次:11[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/400002259/56099
专题北京大学药学院
北京大学药学院_药剂学系
作者单位Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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Yang, Zhenzhen,Xiang, Bai,Dong, Dawen,et al. Dual Receptor-Specific Peptides Modified Liposomes as VEGF siRNA Vector for Tumor-Targeting Therapy[J]. CURRENT GENE THERAPY,2014,14(4):289-299.
APA Yang, Zhenzhen,Xiang, Bai,Dong, Dawen,Wang, Zhanzhang,Li, Jingquan,&Qi, Xianrong.(2014).Dual Receptor-Specific Peptides Modified Liposomes as VEGF siRNA Vector for Tumor-Targeting Therapy.CURRENT GENE THERAPY,14(4),289-299.
MLA Yang, Zhenzhen,et al."Dual Receptor-Specific Peptides Modified Liposomes as VEGF siRNA Vector for Tumor-Targeting Therapy".CURRENT GENE THERAPY 14.4(2014):289-299.
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