|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|
|WOS标题词||Science & Technology|
|关键词[WOS]||CHOROIDAL NEOVASCULARIZATION ; OCULAR NEOVASCULARIZATION ; GENE-TRANSFER ; IN-VIVO ; DELIVERY ; RNAI ; PROTEOGLYCANS ; SUPPRESSION ; DESIGN|
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
|项目编号||2009CB930300 ; 2009ZX09310-001 ; 2007AA021811|
|资助机构||National Basic Research Program of China ; State Key Project ; 863 Project|
|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
|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.|