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Article Abstract
Elevated levels of low-density lipoprotein cholesterol (LDL-C) are a key risk factor contributing to the progression of ischemic heart disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) with small interfering RNA (siRNA) provides an alternative therapeutic option for lowering LDL-C levels. However, the poor pharmacokinetic profiles of naked siRNA hinder clinical application. Herein, we present a siRNA delivery system based on polyamidoamine nanoparticles with galactose-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-modified red blood cell membrane (GRMPS). GRMPS achieved targeted delivery of PCSK9 siRNA to hepatocytes and accumulation of siRNA in the liver for efficient down-regulation of PCSK9 expression and inhibition of LDL receptor, eventually lowering plasma LDL-C level without inducing obvious toxicity. This strategy developed a potential platform for delivering siRNA agents to treat various liver disorders.
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| http://dx.doi.org/10.1016/j.ijpharm.2025.126156 | DOI Listing |
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