Abstract
Due to its small size, easy accessibility and immune privileged environment, the eye represents an ideal target for therapeutic nucleic acids in the treatment of posterior segment ocular diseases, such as age-related macular degeneration (AMD). Among nanocarriers that can be used to achieve nucleic acid delivery, virus-like particles (VLPs) obtained from the Cowpea chlorotic mottle virus (CCMV) are an appealing platform, because of their loading capacity, ease of manufacture and amenability for functionalization. Herein, antisense oligonucleotide-loaded CCMV nanoparticles, intended for intravitreal injection, are evaluated for selective silencing of miR-23, an important target in AMD. CCMV nanoparticles loaded with anti-miR-23 locked nucleic acid and stabilized using the 3,3'-dithiobis(sulfosuccinimidyl propionate) (DTSSP) cross-linker, are assembled in vitro with a loading efficiency up to 80%. VLPs are found to be stable at 37 °C in the vitreous humor up to 24 hours. Nanoparticle cytotoxicity, cellular uptake and transfection efficacy are evaluated in endothelial cells. Selective miRNA down-regulation is achieved by the loaded CCMV VLPs both in absence and presence of Lipofectamine, with efficacies of ≈40% and more than 80%, respectively. The authors' findings pave the way for the future development of CCMV nanoparticles as oligonucleotide delivery platform to treat posterior segment ocular diseases.
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