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.

• Authors: Wei Li, Liang Chen, Zhongwei Gu, Zhoujiang Chen, Hong Li, Zhongxia Cheng, Hanmei Li, Liang Zou
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 355 Pg. 358-370 (03 2023) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 36738972 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Lipid Nanoparticles
• Quercetin
• Peptides
• Angiogenesis Inhibitors
• MicroRNAs
• Mirn150 microRNA, mouse

Topics

• Mice
• Animals
• Quercetin (therapeutic use)
• Endothelial Cells (metabolism)
• Macular Degeneration (drug therapy, metabolism)
• Choroidal Neovascularization (drug therapy)
• Nanoparticles (chemistry)
• Peptides (therapeutic use)
• Angiogenesis Inhibitors (therapeutic use)
• MicroRNAs (therapeutic use)