Reactive Oxygen Species─Responsive Lipid Nanoparticles for Effective RNAi and Corneal Neovascularization Therapy
Anqi Liu, Chunjing Liang, Ji Liu, Yifei Huang, Ming Wang, Liqiang Wang
Abstract
Corneal neovascularization (CNV) is a common disease that affects the vision ability of more than 1 million people annually. Small interfering RNA (siRNA) delivery nanoparticle platforms are a promising therapeutic modality for CNV treatment. However, the efficient delivery of siRNA into cells and the effective release of siRNA from delivery vehicles in a particular cell type challenge effective RNAi clinical application for CNV suppression. This study reports the design of a novel reactive oxygen species (ROS)-responsive lipid nanoparticle for siRNA delivery into corneal lesions for enhanced RNAi as a potential CNV treatment. We demonstrated that lipid nanoparticles could efficiently deliver siRNA into human umbilical vein endothelial cells and release siRNA for enhanced gene silencing by using the upregulated ROS of CNV to promote lipid nanoparticle degradation. Moreover, the subconjunctival injection of siRNA nanocomplexes into corneal lesions effectively knocked down vascular endothelial growth factor expression and suppressed CNV formation in an alkali burn model. Thus, we believe that the strategy of using ROS-responsive lipid nanoparticles for enhanced RNAi in CNV could be further extended to a promising clinical therapeutic approach to attenuate CNV formation.