Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver

• DOI: 10.1126/sciadv.abf4398
• Publication Date: 2021-02-26T20:18:29Z
• Authors: M. Kim; M. Jeong; S. Hur; Y. Cho; J. Park; H. Jung; Y. Seo; H. A. Woo; K. T. Nam; K. Lee; H. Lee
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Liver; 615; Liposomes; 617; Endothelial Cells; Nanoparticles; RNA, Small Interfering; Lipids; Research Articles; 3. Good health

Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations selective certain types liver cells, such as hepatocytes and sinusoidal endothelial cells (LSECs). Here, we report engineered LNPs targeted LSECs. The effects particle size polyethylene glycol-lipid content were evaluated hepatocyte-specific mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted LSECs was further investigated using active ligands. Incorporation mannose allowed LSECs, while minimizing unwanted hepatocytes. These results demonstrate that great potential cell type-specific other tissues.