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

Overview

Journal Nanomaterials (Basel)

Date 2019 Apr 21

PMID 31003493

Citations 11

Authors

Josune Torrecilla

Itziar Gomez-Aguado

Monica Vicente-Pascual

Ana Del Pozo-Rodriguez

Maria Angeles Solinis

Alicia Rodriguez-Gascon

Affiliations

Soon will be listed here.

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.

Citing Articles

Lipid nanoparticle technology-mediated therapeutic gene manipulation in the eyes.

Wang T, Yu T, Liu Q, Sung T, Higuchi A Mol Ther Nucleic Acids. 2024; 35(3):102236.

PMID: 39005878 PMC: 11245926. DOI: 10.1016/j.omtn.2024.102236.

Management of corneal neovascularization: Current and emerging therapeutic approaches.

Wu D, Chan K, Lim B, Lim D, Wong W, Chai C Indian J Ophthalmol. 2024; 72(Suppl 3):S354-S371.

PMID: 38648452 PMC: 467007. DOI: 10.4103/IJO.IJO_3043_23.

Development of Osthole-Loaded Microemulsions as a Prospective Ocular Delivery System for the Treatment of Corneal Neovascularization: In Vitro and In Vivo Assessments.

Zhang Y, Yang J, Ji Y, Liang Z, Wang Y, Zhang J Pharmaceuticals (Basel). 2023; 16(10).

PMID: 37895813 PMC: 10610237. DOI: 10.3390/ph16101342.

Nanomedical research and development in Spain: improving the treatment of diseases from the nanoscale.

Fernandez-Gomez P, Perez de la Lastra Aranda C, Tosat-Bitrian C, Bueso de Barrio J, Thompson S, Sot B Front Bioeng Biotechnol. 2023; 11:1191327.

PMID: 37545884 PMC: 10401050. DOI: 10.3389/fbioe.2023.1191327.

Ocular-Surface Regeneration Therapies for Eye Disorders: The State of the Art.

Posarelli M, Romano D, Tucci D, Giannaccare G, Scorcia V, Taloni A BioTech (Basel). 2023; 12(2).

PMID: 37366796 PMC: 10295950. DOI: 10.3390/biotech12020048.

References

Mohan R, Chintala S, Jung J, Villar W, McCabe F, Russo L . Matrix metalloproteinase gelatinase B (MMP-9) coordinates and effects epithelial regeneration. J Biol Chem. 2001; 277(3):2065-72. DOI: 10.1074/jbc.M107611200. View

Sivak J, Fini M . MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology. Prog Retin Eye Res. 2002; 21(1):1-14. DOI: 10.1016/s1350-9462(01)00015-5. View

Lee S, Zheng M, Kim B, Rouse B . Role of matrix metalloproteinase-9 in angiogenesis caused by ocular infection with herpes simplex virus. J Clin Invest. 2002; 110(8):1105-11. PMC: 150797. DOI: 10.1172/JCI15755. View

Haas T . Endothelial cell regulation of matrix metalloproteinases. Can J Physiol Pharmacol. 2005; 83(1):1-7. DOI: 10.1139/y04-120. View

Kersey J, Broadway D . Corticosteroid-induced glaucoma: a review of the literature. Eye (Lond). 2005; 20(4):407-16. DOI: 10.1038/sj.eye.6701895. View

Azkur A, Kim B, Suvas S, Lee Y, Kumaraguru U, Rouse B . Blocking mouse MMP-9 production in tumor cells and mouse cornea by short hairpin (sh) RNA encoding plasmids. Oligonucleotides. 2005; 15(2):72-84. DOI: 10.1089/oli.2005.15.72. View

Del Pozo-Rodriguez A, Delgado D, Solinis M, Gascon A, Pedraz J . Solid lipid nanoparticles: formulation factors affecting cell transfection capacity. Int J Pharm. 2007; 339(1-2):261-8. DOI: 10.1016/j.ijpharm.2007.03.015. View

Gordon G, Ledee D, Feuer W, Fini M . Cytokines and signaling pathways regulating matrix metalloproteinase-9 (MMP-9) expression in corneal epithelial cells. J Cell Physiol. 2009; 221(2):402-11. PMC: 2990951. DOI: 10.1002/jcp.21869. View

Mukherjee S, Ray S, Thakur R . Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2010; 71(4):349-58. PMC: 2865805. DOI: 10.4103/0250-474X.57282. View

10.

ODoherty M, Murphy C . Update on immunosuppressive therapy for corneal transplantation. Int Ophthalmol Clin. 2010; 50(3):113-22. DOI: 10.1097/IIO.0b013e3181e219a8. View

11.

Kimura K . [Molecular mechanism of the disruption of barrier function in cultured human corneal epithelial cells induced by tumor necrosis factor-alpha, a proinflammatory cytokine]. Nippon Ganka Gakkai Zasshi. 2010; 114(11):935-43. View

12.

Mohan R, Sinha S, Tandon A, Gupta R, Tovey J, Sharma A . Efficacious and safe tissue-selective controlled gene therapy approaches for the cornea. PLoS One. 2011; 6(4):e18771. PMC: 3075266. DOI: 10.1371/journal.pone.0018771. View

13.

Delgado D, Del Pozo-Rodriguez A, Solinis M, Rodriguez-Gascon A . Understanding the mechanism of protamine in solid lipid nanoparticle-based lipofection: the importance of the entry pathway. Eur J Pharm Biopharm. 2011; 79(3):495-502. DOI: 10.1016/j.ejpb.2011.06.005. View

14.

Clements J, Dana R . Inflammatory corneal neovascularization: etiopathogenesis. Semin Ophthalmol. 2011; 26(4-5):235-45. DOI: 10.3109/08820538.2011.588652. View

15.

Mohan R, Tovey J, Sharma A, Tandon A . Gene therapy in the cornea: 2005--present. Prog Retin Eye Res. 2011; 31(1):43-64. PMC: 3242872. DOI: 10.1016/j.preteyeres.2011.09.001. View

16.

Jin X, Sun T, Zhao C, Zheng Y, Zhang Y, Cai W . Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA. Nucleic Acids Res. 2011; 40(4):1797-806. PMC: 3287203. DOI: 10.1093/nar/gkr927. View

17.

Delgado D, Gascon A, Del Pozo-Rodriguez A, Echevarria E, Perez Ruiz de Garibay A, Rodriguez J . Dextran-protamine-solid lipid nanoparticles as a non-viral vector for gene therapy: in vitro characterization and in vivo transfection after intravenous administration to mice. Int J Pharm. 2012; 425(1-2):35-43. DOI: 10.1016/j.ijpharm.2011.12.052. View

18.

Delgado D, Del Pozo-Rodriguez A, Solinis M, Aviles-Triqueros M, Weber B, Fernandez E . Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis. Hum Gene Ther. 2012; 23(4):345-55. DOI: 10.1089/hum.2011.115. View

19.

Yang Y, Wang F, Zhou W, Wu Z, Xing Y . TNF-α stimulates MMP-2 and MMP-9 activities in human corneal epithelial cells via the activation of FAK/ERK signaling. Ophthalmic Res. 2012; 48(4):165-70. DOI: 10.1159/000338819. View

20.

Ueta M, Kinoshita S . Ocular surface inflammation is regulated by innate immunity. Prog Retin Eye Res. 2012; 31(6):551-75. DOI: 10.1016/j.preteyeres.2012.05.003. View