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学科主题: 药学
题名:
Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas
作者: Yang, Zhen-Zhen; Li, Jing-Quan; Wang, Zhan-Zhang; Dong, Da-Wen; Qi, Xian-Rong
关键词: Angiopep-2 ; tLyP-1 ; Dual peptides-modified liposomes ; Combination therapy ; VEGF ; Docetaxel
刊名: BIOMATERIALS
发表日期: 2014-06-01
DOI: 10.1016/j.biomaterials.2014.03.017
卷: 35, 期:19, 页:5226-5239
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]: Engineering ; Materials Science
关键词[WOS]: DENSITY-LIPOPROTEIN RECEPTOR ; ENDOTHELIAL GROWTH-FACTOR ; DRUG-DELIVERY ; CANCER-CELLS ; INTERFERING RNA ; CO-DELIVERY ; NANOPARTICLES ; NANOCARRIERS ; DOXORUBICIN ; THERAPY
英文摘要:

Combinations of drugs promoting anti-angiogenesis and apoptosis effects are meaningful for cancer therapy. In the present study, dual peptides-modified liposomes were designed by attaching two receptor-specific peptides, specifically low-density lipoprotein receptor-related protein receptor (Angiopep-2) and neuropilin-1 receptor (tLyP-1) for brain tumor targeting and tumor penetration. Vascular endothelial growth factor (VEGF) siRNA and chemotherapeutic docetaxel (DTX) were chosen as the two payloads because VEGF is closely associated with angiogenesis, and DTX can kill tumor cells efficiently. Binding to glioma cells, co-delivery of siRNA and DTX in human glioblastoma cells (U87 MG) and murine brain microvascular endothelial cells (BMVEC), VEGF gene silencing, antiproliferation and anti-tumor effects of the dual peptides-modified liposomes were evaluated in vitro and in vivo. The dual peptides-modified liposomes persisted the binding ability to glioma cells, enhanced the internalization via specific receptor mediated endocytosis and tissue penetration, thus the dual peptides-modified liposomes loading VEGF siRNA and DTX possessed stimulative gene silencing and antiproliferation activity compared with non-modified and single peptide-modified liposomes. The co-delivery research revealed different intracellular behavior of hydrophilic large molecular and lipophilic small molecule, the former involves endocytosis and subsequent escape of endosome/lysosomes, while the latter experiences passive diffusion of lipophilic small drugs after its release. Furthermore, the dual peptides-modified liposomes showed superiority in anti-tumor efficacy, combination of anti-angiogenesis by VEGF siRNA and apoptosis effects by DTX, after both intratumor and system application against mice with U87 MG tumors, and the treatment did not activate system-associated toxicity or the innate immune response. Combination with the dual peptides-guided tumor homing and penetration, the dual peptides-modified liposomes provide a strategy for effective targeting delivery of siRNA and DTX into the glioma cell and inhibition of tumor growth in a synergistic manner. (c) 2014 Elsevier Ltd. All rights reserved.

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:000335705600019
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58963
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, Zhen-Zhen,Li, Jing-Quan,Wang, Zhan-Zhang,et al. Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas[J]. BIOMATERIALS,2014,35(19):5226-5239.
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