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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
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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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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