4.8 Article

Co-delivery of microRNA-150 and quercetin by lipid nanoparticles (LNPs) for the targeted treatment of age-related macular degeneration (AMD)

期刊

JOURNAL OF CONTROLLED RELEASE
卷 355, 期 -, 页码 358-370

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ELSEVIER
DOI: 10.1016/j.jconrel.2023.01.080

关键词

lipid nanoparticles (LNPs); Quercetin; NGR peptide; Age-related macular degeneration; Choroidal neovascularization

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Age-related macular degeneration (AMD) is a disease that causes severe vision loss in middle-aged and elderly patients due to choroidal neovascularization (CNV). Current treatments for CNV are ineffective and can have adverse effects. This study developed solid lipid nanoparticles modified with an Asp-Gly-Arg peptide to target endothelial cells during abnormal angiogenesis. These nanoparticles successfully co-delivered microRNA-150 (mR150) and the antiangiogenic drug quercetin, inhibiting CNV without retinal toxicity in a mouse model.
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 posttranscriptional 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 antiangiogenic 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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