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Effect of the array of amines on the transfection efficiency of cationic peptidomimetic lipid molecules into neural cells
RSC Advances ( IF 3.9 ) Pub Date : 2022-08-03 , DOI: 10.1039/d2ra03347j
Xiang Yu 1 , Hai Xiao 1 , Muqier Muqier 1 , Shuqin Han 1 , Huricha Baigude 1
Affiliation  

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.

中文翻译:

胺阵列对阳离子拟肽脂质分子转染神经细胞效率的影响

阳离子脂质头基中的氨基对于由脂质配制的 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化头基的脂质,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处缀合乙氨基会产生 4 种不同的脂质,其中具有 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, 分别。流式细胞术比较分析表明,N3脂质对神经细胞系(BV2细胞和N2a细胞)的核酸(质粒和siRNA)转染效率最高。此外,N3脂质介导将针对Toll样受体4(TLR4)的siRNA递送至氧糖剥夺(OGD)处理的BV2细胞中,导致TLR4显着沉默,诱导细胞的交替极化(M2)。总的来说,我们的数据表明 N3 脂质是神经细胞中一种有前途的 siRNA 递送剂。
更新日期:2022-08-03
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