Inhibition of retinal neovascularization by VEGF siRNA delivered via bioreducible lipid-like nanoparticles
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Inhibition of retinal neovascularization by VEGF siRNA delivered via bioreducible lipid-like nanoparticles Zonghua Wang 1,2 & Anqi Liu 1,3 & Han Zhang 4 & Ming Wang 5,6 & Qiao Tang 5,6 & Yifei Huang 1 & Liqiang Wang 1 Received: 10 February 2020 / Revised: 2 June 2020 / Accepted: 8 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Retinopathy of prematurity . Ranibizumab . VEGF . RNA interference . Retinal neovascularization . Lipidoid nanocomplex Zonghua Wang and Anqi Liu are the Co-first authors.
Introduction * Yifei Huang [email protected] * Liqiang Wang [email protected] 1
Department of Ophthalmology, Chinese People’s Liberation Army General Hospital, Fuxing Road 28, Beijing 100853, China
2
Department of Ophthalmology, The Seventh Medical center of PLA General Hospital, Beijing 100700, China
3
The Chinese People’s Liberation Army NO.32141, Beijing, China
4
The 2nd Hospital of Shandong University, 247 Beiyuan Road, Jinan 250031, China
5
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100049, China
6
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, the Chinese Academy of Sciences (CAS), Beijing 100190, China
Retinal neovascularization (RNV) can be triggered by retinal hypoxia and ischemia, and its natural hist
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