Yu Xiang, Xiao Hai, Muqier Muqier, Han Shuqin, Baigude Huricha
School of Chemistry & Chemical Engineering, Inner Mongolia University Hohhot Inner Mongolia 010020 P.R. China +86 471 4992511 +86 471 4992511
RSC Adv. 2022 Aug 3;12(33):21567-21573. doi: 10.1039/d2ra03347j. eCollection 2022 Jul 21.
The amino groups in the head group of a cationic lipid play a determinative role regarding the nucleic acid delivery efficiency of the LNP formulated from lipids. Herein, we designed four types of lipid bearing different amine-containing branched head groups to investigate the influence of type and number of amines on the neural cell targeted nuclei acid delivery. Conjugation of an ethylamino group at selected positions of a lysine-based cationic lipid resulted in 4 distinct lipids with 3 (denoted N3 lipid), 4 (denoted N4 lipid), 5 (denoted N5 lipid) and 6 (denoted N6 lipid) amino groups, respectively. Comparative analysis by flow cytometry revealed that the N3 lipid had the highest nucleic acid (plasmid and siRNA) transfection efficiency to neural cell lines (BV2 cells and N2a cells). Furthermore, the N3 lipid mediated delivery of siRNA against Toll Like Receptor 4 (TLR4) into oxygen glucose deprivation (OGD)-treated BV2 cells resulted in remarkable silencing of TLR4, inducing alternative polarization (M2) of the cells. Collectively, our data suggest that the N3 lipid is a promising siRNA delivery agent in neural cells.
阳离子脂质头部基团中的氨基对于由脂质配制的脂质纳米颗粒（LNP）的核酸递送效率起着决定性作用。在此，我们设计了四种带有不同含胺支链头部基团的脂质，以研究胺的类型和数量对神经细胞靶向核酸递送的影响。在基于赖氨酸的阳离子脂质的选定位置缀合乙氨基，分别产生了具有3个（表示为N3脂质）、4个（表示为N4脂质）、5个（表示为N5脂质）和6个（表示为N6脂质）氨基的4种不同脂质。通过流式细胞术进行的比较分析表明，N3脂质对神经细胞系（BV2细胞和N2a细胞）具有最高的核酸（质粒和siRNA）转染效率。此外，N3脂质介导的针对Toll样受体4（TLR4）的siRNA递送至氧葡萄糖剥夺（OGD）处理的BV2细胞中，导致TLR4显著沉默，诱导细胞发生交替极化（M2）。总体而言，我们的数据表明N3脂质是一种有前景的神经细胞siRNA递送剂。
