可电离脂质及其对载核酸药物脂质纳米粒转染效率和安全性的影响研究进展OA北大核心CSTPCD

Lipid nanoparticles(LNPs),composed of ionizable lipids,are currently the most promis-ing non-viral nucleic acid drug delivery vectors in clinical practice,and have great potential in gene ther-apy drug delivery and vaccine delivery.Ionizable lipids,the main components of LNPs,play a decisive role in the endosome escape rate,transfection efficiency,organ targeting and safety of LNPs.Among them,the hydrophilic head group of ionizable lipids contains tertiary amine groups,which can improve the buffering capacity of LNPs and thus change the pKa value,and imidazole can enhance the stability and transfection activity of mRNA-LNP.The ligand contains ester groups,which can induce gene silencing efficiently and improve the degradation rate and safety.When the number of hydrophobic tails is 3-4,with 1-2 unsaturation and 8-18 carbon chain length,LNPs can effectively induce gene silencing.Meanwhile,the presence of branching or asymmetric hydrophobic tails can improve the transfection efficiency of LNPs.Based on the chemical structure of ionizable lipids,this review summarizes the influ-ence of the structure of ionizable lipids on the transfection efficiency and safety of nucleic acid carrying drugs LNPs,and the structure-activity relationship of ionizable lipids so as to provide reference for studies on novel ionizable lipids.