Chenodeoxycholic Acid-Modified Polyethyleneimine Nano-Composites Deliver Low-Density Lipoprotein Receptor Genes for Lipid-Lowering Therapy by Targeting the Liver.

Lipid-lowering drugs, especially statins, have been extensively utilized in clinical settings for the prevention of hyperlipidemia. Nevertheless, prolonged usage of current lipid-lowering medications is associated with significant adverse reactions. Therefore, it is imperative to develop novel therapeutic agents for lipid-lowering therapy. In this study, we synthesized a chenodeoxycholic acid and lactobionic acid double-modified polyethyleneimine (PDL) nanocomposite as a gene delivery vehicle for lipid-lowering therapy by targeting the liver. Results from the in vitro experiments demonstrate that PDL exhibits superior transfection efficiency compared to polyethyleneimine in AML12 cells and effectively carries plasmids. Moreover, PDL can be internalized by AML12 cells and rapidly escape lysosomal entrapment. Intravenous administration of Cy5.5-conjugated PDL nanocomposites reveals their preferential accumulation in the liver compared to polyethyleneimine counterparts. Systemic delivery of low-density lipoprotein receptor plasmid-loaded PDL nanocomposites into mice leads to reduced levels of low-density lipoprotein cholesterol and triglycerides in the bloodstream without any observed adverse effects on mouse health or well-being. Collectively, our findings suggest that low-density lipoprotein receptor plasmid-loaded PDL nanocomposites hold promise as potential therapeutics for lipid-lowering therapy. This article is protected by copyright. All rights reserved.

Informations de copyright

This article is protected by copyright. All rights reserved.