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

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

doi:10.1016/j.bmc.2024.118008

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

Bioorg Med Chem. 2024 Nov 16:118:118008. doi: 10.1016/j.bmc.2024.118008. Online ahead of print.

Authors

Guoqing Feng¹, Yang Bai², Pengyu Huang³, Yuan Liu⁴, Qingbin Yang¹, Bowen Li¹, Qing Yuan⁵, Niansong Qian⁶, Bin Zheng⁷

Affiliations

¹ Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.
² Department of Stomatology, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, China; Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China. Electronic address: [email protected].
³ Fujian Provincial Sperm Bank, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China.
⁴ Tianjin Anding Hospital, Tianjin 300222, China.
⁵ Department of Urology, The Third Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, China.
⁶ Department of Respiratory, the Eighth Medical Center of Chinese PLA General Hospital, Beijing 100853, China. Electronic address: [email protected].
⁷ Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China; School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, 300070, China. Electronic address: [email protected].

PMID: 39637443
DOI: 10.1016/j.bmc.2024.118008

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.

Keywords: Cationic lipid; Gene delivery; Optogenetic manipulation; Polycations; Polyethyleneimine (PEI).