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Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis
Ding, Yang1; Wang, Yazhe1; Zhou, Jianping1; Gu, Xiaochen2; Wang, Wei1; Liu, Congyan1; Bao, Xiuli1; Wang, Cheng1; Li, Yuanru1; Zhang, Qiang3
关键词Reconstituted High Density Lipoprotein Cholesterol-conjugated Sirna Direct Cytosolic Delivery Vascular Endothelial Growth Factor Tumor-selective Accumulation Anti-angiogenic Therapy
刊名BIOMATERIALS
2014-08-01
DOI10.1016/j.biomaterials.2014.05.009
35期:25页:7214-7227
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]POLYELECTROLYTE COMPLEX MICELLES ; APOLIPOPROTEIN-A-I ; SCAVENGER RECEPTOR ; ANTICANCER DRUGS ; RNA INTERFERENCE ; SELECTIVE UPTAKE ; CANCER-THERAPY ; BREAST-CANCER ; NANOPARTICLES ; CELLS
英文摘要

We described here the mechanisms by which small interfering RNA (siRNA) molecules incorporated in reconstituted high density lipoprotein (rHDL) were efficiently transferred into the cytoplasm of cells to perform target-specific therapy of tumor angiogenesis. Using fluorescent-tagged apolipoprotein A-I (apoA-I) and cholesterol-conjugated siRNA (Chol-siRNA), it was confirmed with FACS and confocal microscopic measurements that Chol-siRNA-loaded rHDL nanoparticles (rHDL/Chol-siRNA complexes) were successfully established and apoA-I certainly was attached to the surface of Chol-siRNA-loaded lipoplexes (Lipos/Chol-siRNA complexes). Stably assembled rHDL/Chol-siRNA complexes demonstrated proper nanosize, quasi-spherical shape and improved nuclease protection over naked Chol-siRNA. It was also interesting to note that rHDL provided a highly effective approach to transfer Chol-siRNA across the membrane directly into the cytoplasm via the scavenger receptor BI (SR-BI)-mediated non-endocytotic mechanism, thereby bypassing endo-lysosomal trapping. We also showed clear evidence that the in vitro implementation of rHDL for Chol-siRNA-VEGF (Chol-siRNA targeting vascular endothelial growth factor gene) delivery markedly promoted RNA interference (RNAi)-mediated degradation of VEGF mRNA, resulting in down-regulation of secreted VEGF protein. In vivo fluorescence imaging indicated that near-infrared (NIR) dye Cy5 labeled Chol-siRNA-loaded rHDL nanoparticles (rHDL/Cy5-Chol-5iRNA complexes) displayed long circulation time, SR-BI positive tumor-selective targeting, and efficient cytosolic delivery capabilities. Furthermore, intravenous administration of Chol-siRNA-VEGF-loaded rHDL nanoparticles (rHDL/Chol-siRNA-VEGF complexes) significantly enhanced anti-tumor efficacy against breast cancer, decreased VEGF expression level, and inhibited formation of intratumoral microvessels at the tumor tissue. It was concluded that rHDL possessed therapeutic potential and versatility in mediating CholsiRNA-VEGF direct cytosolic delivery for target-specific anti-angiogenic therapy in breast cancer. (C) 2014 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000338386800052
项目编号81102398 ; 81273469 ; BK2011624 ; 20110096120003 ; JKVD2013011 ; CXZZ12_0316 ; SDD2012-03 ; SKLNMKF201305 ; J1030830
资助机构National Natural Science Foundation of China ; Natural Science Foundation of Jiangsu Province ; Ministry of Education Doctoral Program of Higher Specialized Research Fund project ; Fundamental Research Funds for the Central Universities ; Graduate Cultivation Innovative Project of Jiangsu Province ; School of Pharmacy, Fudan University &amp ; The Open Project Program of Key Lab of Smart Drug Delivery (Fudan University), Ministry of Education, China ; Open Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University ; National Found for Fostering Talents of Basic Science
引用统计
被引频次:41[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/400002259/56143
专题北京大学药学院
北京大学药学院_药剂学系
作者单位1.Univ Manitoba, Fac Pharm, Winnipeg, MB R3E 0T5, Canada
2.China Pharmaceut Univ, Dept Pharmaceut, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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GB/T 7714
Ding, Yang,Wang, Yazhe,Zhou, Jianping,et al. Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis[J]. BIOMATERIALS,2014,35(25):7214-7227.
APA Ding, Yang.,Wang, Yazhe.,Zhou, Jianping.,Gu, Xiaochen.,Wang, Wei.,...&Zhang, Qiang.(2014).Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis.BIOMATERIALS,35(25),7214-7227.
MLA Ding, Yang,et al."Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis".BIOMATERIALS 35.25(2014):7214-7227.
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