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A Lipid Nanoparticle System Improves siRNA Efficacy in RPE Cells and a Laser-Induced Murine CNV Model
Liu, Hong-an1; Liu, Yu-ling1; Ma, Zhi-zhong1; Wang, Jian-cheng2; Zhang, Qiang2
刊名INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2011-06-01
DOI10.1167/iovs.10-5891
52期:7页:4789-4794
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Ophthalmology
研究领域[WOS]Ophthalmology
关键词[WOS]CHOROIDAL NEOVASCULARIZATION ; OCULAR NEOVASCULARIZATION ; GENE-TRANSFER ; IN-VIVO ; DELIVERY ; RNAI ; PROTEOGLYCANS ; SUPPRESSION ; DESIGN
英文摘要

PURPOSE. To explore the possibility of the PEGylated liposome-protamine-hyaluronic acid nanoparticles (PEG-LPH-NP) loaded with siRNA (PEG-LPH-NP-S) in ARPE19 cells and a laser-induced rat model for the treatment of choroidal neovascularization (CNV).

METHODS. PEG-LPH-NP-S was characterized by dynamic light scattering and transmission electron microscopy (TEM). The encapsulation efficiency of siRNA in PEG-LPH-NP was analyzed by ultracentrifugation, whereas the protection of siRNA by PEG-LPH-NP was evaluated by electrophoresis. Human RPE cells (ARPE19) were used as the cell model for the studies of cellular uptake and the inhibition of VEGFR1 expression, visualized by a laser scanning confocal microscope. The area of CNV in the laser-induced rat model after intravitreous injection was measured. The distribution of the lipid nanoparticles in the retina after intravitreous administration was investigated by fluorescence microscopy. Finally, the TUNEL test and morphologic observation of the retina were conducted.

RESULTS. It was indicated that PEG-LPH-NP-S was approximately 132 nm in particle size with a positive charge of approximately 20 mV, whereas the encapsulation efficiency of siRNA in PEG-LPH-NP was >95%. PEG-LPH-NP could protect the siRNA load and could facilitate the intracellular delivery of fluorescein-labeled siRNA to ARPE19 cells. VEGFR1 expression in ARPE19 cells could be inhibited, and the CNV area in the murine model could be reduced more effectively by PEG-LPH-NP-S compared with naked siRNA and by PEG-LPH-NP with negative siRNA. It seems that the toxicity of PEG-LPH-NP-S on the rat retina is low, based on the results of TUNEL testing and morphologic observation.

CONCLUSIONS. PEG-LPH-NP may be a promising lipid nanoparticle system for the siRNA treatment of CNV. (Invest Ophthalmol Vis Sci. 2011;52:4789-4794) DOI:10.1167/iovs.10-5891

语种英语
WOS记录号WOS:000293332500114
项目编号2009CB930300 ; 2009ZX09310-001 ; 2007AA021811
资助机构National Basic Research Program of China ; State Key Project ; 863 Project
引用统计
被引频次:39[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/400002259/64542
专题北京大学第三临床医学院_眼科
北京大学基础医学院
作者单位1.Peking Univ, Peking Univ Eye Ctr, Peking Univ Hosp 3, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
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GB/T 7714
Liu, Hong-an,Liu, Yu-ling,Ma, Zhi-zhong,et al. A Lipid Nanoparticle System Improves siRNA Efficacy in RPE Cells and a Laser-Induced Murine CNV Model[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2011,52(7):4789-4794.
APA Liu, Hong-an,Liu, Yu-ling,Ma, Zhi-zhong,Wang, Jian-cheng,&Zhang, Qiang.(2011).A Lipid Nanoparticle System Improves siRNA Efficacy in RPE Cells and a Laser-Induced Murine CNV Model.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,52(7),4789-4794.
MLA Liu, Hong-an,et al."A Lipid Nanoparticle System Improves siRNA Efficacy in RPE Cells and a Laser-Induced Murine CNV Model".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 52.7(2011):4789-4794.
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