Charge-neutralized polyethylenimine-lipid nanoparticles for gene transfer to human embryonic stem cells.

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic & Medicinal Chemistry Pub Date : 2025-02-01 Epub Date: 2024-11-16 DOI:10.1016/j.bmc.2024.118008

Guoqing Feng, Yang Bai, Pengyu Huang, Yuan Liu, Qingbin Yang, Bowen Li, Qing Yuan, Niansong Qian, Bin Zheng

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Abstract

Gene delivery is fundamentally crucial for the genetic manipulation of stem cells. Here, we present a straightforward approach to create a library of charge-neutralized polyethylenimine (PEI)-lipid nanoparticles designed for stem cell transfection. These lipid nanoparticles were formulated using small, branched PEI and lipidic anhydrides. Remarkably, over 15% of the lipid nanoparticles demonstrated high transfection efficiency across various cell types, surpassing the efficiency of both Lipofectamine 2000 and FuGENE HD. A structure-activity analysis indicated that the length and ratio of hydrophobic alkyl substitutions were critical parameters for efficient gene delivery. Notably, the transfection efficiency was higher than that of the original cation PEI. Our optimized PEI-lipid system enabled highly effective plasmid DNA delivery and successfully co-transferred two plasmid DNAs into difficult-to-transfect human embryonic stem cells (hESCs), facilitating optogenetic manipulation within these cells.

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用于人胚胎干细胞基因转移的电荷中和聚乙烯亚胺脂纳米颗粒。

基因传递对于干细胞的基因操作至关重要。在这里，我们提出了一种直接的方法来创建一个用于干细胞转染的电荷中和聚乙烯亚胺（PEI）脂质纳米颗粒库。这些脂质纳米颗粒是用小的，支化的PEI和脂质酸酐配制的。值得注意的是，超过15%的脂质纳米颗粒在各种细胞类型中表现出较高的转染效率，超过了Lipofectamine 2000和FuGENE HD的效率。结构-活性分析表明，疏水烷基取代的长度和比例是有效传递基因的关键参数。值得注意的是，转染效率高于原阳离子PEI。我们优化的pei -脂质系统实现了高效的质粒DNA传递，并成功地将两个质粒DNA共转移到难以转染的人胚胎干细胞（hESCs）中，促进了这些细胞内的光遗传学操作。

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.