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- Title
Inhibition of retinal neovascularization by VEGF siRNA delivered via bioreducible lipid-like nanoparticles.
- Authors
Wang, Zonghua; Liu, Anqi; Zhang, Han; Wang, Ming; Tang, Qiao; Huang, Yifei; Wang, Liqiang
- Abstract
Purpose: Previously, we have demonstrated the use of lipidoid (lipid-like) nanoparticles (e.g., "1-O16B") for gene delivery to live cells, as an alternative to viral vectors. Here, we encapsulate VEGF siRNA (siVEGF) in bioreducible lipidoid nanoparticles and examine whether these nanocomplexes can reduce intravitreal neovascularization in a rodent model of oxygen-induced retinopathy (OIR). Methods: Firstly, we constructed siVEGF-nanoparticles (NPs) and transfected human umbilical vein endothelial cells, which caused significantly reduced expression of VEGF, compared to exposure to siVEGF in solution. Secondly, we compared the effect of intravitreal siVEGF-NPs and an anti-VEGF drug (ranibizumab) on retinal vascular development and VEGF mRNA/protein expression in the retinas of a rat model of OIR. Results: Compared to a non-functional lipid vehicle control group, the level of VEGF mRNA and protein was significantly lower in the siVEGF-NP group (p < 0.01), but the level of VEGF mRNA was not significantly lower in the ranibizumab group. Anatomically, the number of retinal neovascular endothelial nuclei that had protruded through the internal limiting membrane and the number of areas of non-perfusion of the retina were both significantly lower in the siVEGF-NP group and the ranibizumab group than in the OIR group (p < 0.01). Conclusion: Our results demonstrate that bioreducible lipidoid nanoparticles conveying VEGF siRNA can effectively inhibit retinal neovascularization in a rodent model of OIR, and reduce the expression of VEGF mRNA and protein. This novel treatment modality could have profound implications for treating retinal angiogenic diseases.
- Subjects
RANIBIZUMAB; VASCULAR endothelial growth factor antagonists; NEOVASCULARIZATION; GENETIC vectors; SMALL interfering RNA; NANOPARTICLES; UMBILICAL veins
- Publication
Graefe's Archive of Clinical & Experimental Ophthalmology, 2020, Vol 258, Issue 11, p2407
- ISSN
0721-832X
- Publication type
Article
- DOI
10.1007/s00417-020-04797-3