内体
核酸
合理设计
胞浆
细胞质
阳离子聚合
化学
药物输送
细胞生物学
生物物理学
生物化学
纳米技术
生物
酶
细胞
材料科学
有机化学
作者
Kaitlin Mrksich,Marshall S. Padilla,Michael J. Mitchell
标识
DOI:10.1016/j.addr.2024.115446
摘要
In the past decade, nucleic acid therapies have seen a boon in development and clinical translation largely due to advances in nanotechnology that have enabled their safe and targeted transport. Nanoparticles can protect nucleic acids from degradation by serum enzymes and can facilitate entry into cells. Still, achieving endosomal escape to allow the nucleic acids to enter the cytoplasm has remained a significant barrier, where less than 5% of particles within the endo-lysosomal pathway are able to transfer their cargo to the cytosol. Lipid-based drug delivery vehicles, particularly lipid nanoparticles (LNPs), have been optimized to achieve potent endosomal escape, and thus have been the vector of choice in the clinic as demonstrated by their utilization in the COVID-19 mRNA vaccines. The success of LNPs is in large part due to the rational design of lipids that can specifically break through endosomal barriers. In this review, we chart the evolution of lipid structure from cationic lipids to ionizable lipids, focusing on structure-function relationships, especially as they relate to endosomal escape. Additionally, we examine recent advancements in ionizable lipid structure as well as discuss the future of lipid design.
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