Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Kim, M.; Jeong, M.; Jung, H.; Seo, Y.; Woo, H. A.; Lee, K.; Lee, H.] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 120750, South Korea; [Hur, S.; Cho, Y.; Nam, K. T.] Yonsei Univ, Severance Biomed Sci Inst, Brain Korea 21 PLUS Project Med Sci, Coll Med, Seoul 03722, South Korea; [Park, J.] Ewha Womans Univ, Fluorescence Core Imaging Ctr, Seoul 120750, South Korea; [Lee, K.] Gyeongsang Natl Univ, Coll Pharm, Jinju 52828, South Korea; [Lee, K.] Gyeongsang Natl Univ, Res Inst Pharmaceut Sci, Jinju 52828, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 AMER ASSOC ADVANCEMENT SCIENCE
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000181422
- 본문언어 영어
- Published As http://dx.doi.org/10.1126/sciadv.abf4398
초록/요약
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 for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol-lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type-specific delivery of RNA into the liver and other tissues.
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