Co-delivery of microRNA-150 and quercetin by lipid nanoparticles (LNPs) for the targeted treatment of age-related macular degeneration (AMD)
Abstract
Age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), which leads to severe vision loss in middle-aged and elderly patients. Current treatments for CNV show weak, transient efficacy, and they can cause several adverse effects. A potential new treatment is to use microRNA-150 (mR150), which regulates physiological and pathological angiogenesis by modulating the expression of CXCR4 at the post-transcriptional level. Here, we developed solid lipid nanoparticles that we modified with an Asp-Gly-Arg peptide to target endothelial cells during abnormal angiogenesis, then we co-loaded them with mR150 and the anti-angiogenic drug quercetin. The resulting nanoparticles had an average size around 200 nm and showed strong ability to target the fundus and inhibit CNV for up to two weeks in a mouse model without causing retinal toxicity. They significantly enhanced the uptake of mR150 in vitro compared to free mR150 or nanoparticles without peptide. Our study suggests that co-administration of mR150 and quercetin has potential for treating age-related macular degeneration and that nanoparticles modified with Asp-Gly-Arg peptide are an effective platform for the co-delivery of small-molecule and nucleic acid drugs via intravitreal injection.
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