MMP-9 Downregulation with Lipid Nanoparticles for Inhibiting Corneal Neovascularization by Gene Silencing
AbstractGene 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
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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.
Torrecilla J, Gómez-Aguado I, Vicente-Pascual M, del Pozo-Rodríguez A, Solinís MÁ, Rodríguez-Gascón A. MMP-9 Downregulation with Lipid Nanoparticles for Inhibiting Corneal Neovascularization by Gene Silencing. Nanomaterials. 2019; 9(4):631.Chicago/Turabian Style
Torrecilla, Josune; Gómez-Aguado, Itziar; Vicente-Pascual, Mónica; del Pozo-Rodríguez, Ana; Solinís, María Á.; Rodríguez-Gascón, Alicia. 2019. "MMP-9 Downregulation with Lipid Nanoparticles for Inhibiting Corneal Neovascularization by Gene Silencing." Nanomaterials 9, no. 4: 631.
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