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Therapeutic effects of a novel siRNA-based anti-VEGF (siVEGF) nanoball for the treatment of choroidal neovascularization

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries and is characterized by the development of choroidal neovascularization (CNV). Therapies for AMD have focused on suppressing angiogenic factors, such as vascular endothelial growth factor (VEGF), mainly via conventional antI-VEGF antibody agents. However, additional efforts have been made to develop effective small-interfering RNA (siRNA)-based intracellular therapeutic agents. In this study, we have manufactured a novel siRNA-based anti-VEGF nanoball (siVEGF NB). The siVEGF NB was composed of siRNA hydrogel with a core of anti-VEGF sequence siRNA coated with branched PEI (bPEI) and hyaluronic acid (HA) one by one by electrical force. The novel siVEGF NBs, which were applied to a laser-induced CNV mouse model, were optimized as a retinal and choroidal delivery system through the vitreous humor to the sub-retinal space via CD44 receptor endocytosis on the inner limiting membrane, and showed therapeutic effects via pathways bypassing the TLR3-induced siRNA-class effect. The therapeutic effects of siVEGF NBs lasted for 2 weeks after intravitreal injection showing high targeting efficiency to the sub-retinal space. Thus, the newly developed siVEGF NB may have great potential in the delivery of RNAi-based therapeutics for ocular diseases, including AMD.

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Publication details

The article was received on 03 May 2017, accepted on 07 Sep 2017 and first published on 12 Sep 2017


Article type: Paper
DOI: 10.1039/C7NR03142D
Citation: Nanoscale, 2017, Accepted Manuscript
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    Therapeutic effects of a novel siRNA-based anti-VEGF (siVEGF) nanoball for the treatment of choroidal neovascularization

    N. Ryoo, J. Lee, H. Lee, H. K. Hong, H. Kim, J. B. Lee, S. J. Woo, K. Park and H. Kim, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR03142D

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