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Open AccessArticle

MMP-9 Downregulation with Lipid Nanoparticles for Inhibiting Corneal Neovascularization by Gene Silencing

Pharmacokinetic, Nanotechnology & Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01015 Vitoria-Gasteiz, Spain
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Nanomaterials 2019, 9(4), 631; https://doi.org/10.3390/nano9040631
Received: 25 March 2019 / Revised: 12 April 2019 / Accepted: 16 April 2019 / Published: 18 April 2019
Gene silencing targeting proangiogenic factors have been shown to be a useful strategy in the treatment of corneal neovascularization (CNV). Among interference RNA (RNAi) molecules, short-hairpin RNA (shRNA) is a plasmid-coded RNA able to down-regulate the expression of the desired gene. It is continuously produced in the host cell, inducing a durable gene silencing effect. The aim of this work was to develop a solid lipid nanoparticle (SLN)-based shRNA delivery system to downregulate metalloproteinase 9 (MMP-9), a proangiogenic factor, in corneal cells for the treatment of CNV associated with inflammation. The nanovectors were prepared using a solvent emulsification-evaporation technique, and after physicochemical evaluation, they were evaluated in different culture cell models. Transfection efficacy, cell internalization, cell viability, the effect on MMP-9 expression, and cell migration were evaluated in human corneal epithelial cells (HCE-2). The inhibition of tube formation using human umbilical vein endothelial cells (HUVEC) was also assayed. The non-viral vectors based on SLN were able to downregulate the MMP-9 expression in HCE-2 cells via gene silencing, and, consequently, to inhibit cell migration and tube formation. These results demonstrate the potential of lipid nanoparticles as gene delivery systems for the treatment of CNV-associated inflammation by RNAi technology. View Full-Text
Keywords: gene therapy; solid lipid nanoparticles; MMP-9; corneal inflammation; HCE-2 cells; capillary tube formation; RNAi; shRNA gene therapy; solid lipid nanoparticles; MMP-9; corneal inflammation; HCE-2 cells; capillary tube formation; RNAi; shRNA
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MDPI and ACS Style

Torrecilla, J.; Gómez-Aguado, I.; Vicente-Pascual, M.; del Pozo-Rodríguez, A.; Solinís, M.Á.; Rodríguez-Gascón, A. MMP-9 Downregulation with Lipid Nanoparticles for Inhibiting Corneal Neovascularization by Gene Silencing. Nanomaterials 2019, 9, 631.

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