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

0303 health sciences 03 medical and health sciences Liver 615 Liposomes 617 Endothelial Cells Nanoparticles RNA, Small Interfering Lipids Research Articles
DOI: 10.1126/sciadv.abf4398 Publication Date: 2021-02-26T20:18:29Z
ABSTRACT
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.
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