Retinopathy of prematurity (ROP) is characterized by pathological angiogenesis and associated inflammation in the retina and is the leading cause of childhood blindness. MiRNA-223 (miR-223) drives microglial polarization toward the anti-inflammatory phenotype and offers a therapeutic approach to suppress inflammation and consequently pathological neovascularization. However, miRNA-based therapy is hindered by the low stability and non-specific cell-targeting ability of delivery systems. In the present study, we developed folic acid-chitosan (FA-CS)-modified mesoporous silica nanoparticles (PMSN) loaded with miR-223 to regulate retinal microglial polarization. The FA-CS/PMSN/miR-223 nanoparticles exhibited high stability and loading efficiency, achieved targeted delivery, and successfully escaped from lysosomes. In cultured microglial cells, treatment with FA-CS/PMSN/miR-223 nanoparticles upregulated the anti-inflammatory gene YM1/2 and IL-4RA, and downregulated the proinflammatory genes iNOS, IL-1β, and IL-6. Notably, in a mouse oxygen-induced retinopathy model of ROP, intravitreally injected FA-CS/PMSN/miR-223 nanoparticles (1 μg) decreased the retinal neovascular area by 52.6%. This protective effect was associated with the reduced and increased levels of pro-inflammatory (M1) and anti-inflammatory (M2) cytokines, respectively. Collectively, these findings demonstrate that FA-CS/PMSN/miR-223 nanoparticles provide an effective therapeutic strategy for the treatment of ROP by modulating the miR-223-mediated microglial polarization to the M2 phenotype.
Keywords: Anti-inflammatory; MiRNA-223-based nanoplatform; Microglial polarization; Neovascularization; Retinopathy of prematurity.
Copyright © 2022. Published by Elsevier B.V.