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学科主题: 药学
题名:
Dual Receptor-Specific Peptides Modified Liposomes as VEGF siRNA Vector for Tumor-Targeting Therapy
作者: 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
发表日期: 2014
卷: 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
所属项目编号: 2013CB932501 ; 81273454 ; 7132113 ; 20100001110056 ; 20130001110055 ; BMU20110263
项目资助者: National Basic Research Program ; NSFC ; Beijing NSF ; Doctoral Foundation of the Ministry of Education ; Innovation Team of Ministry of Education
WOS记录号: WOS:000341362700005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56099
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
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.
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