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

Bioorg Med Chem

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:

Published: November 2024

AI Article Synopsis

  • Gene delivery is essential for modifying stem cells, and this study introduces a new method for creating charge-neutralized polyethylenimine (PEI)-lipid nanoparticles aimed at improving stem cell transfection.
  • The research shows that over 15% of these nanoparticles achieved high transfection efficiency across different cell types, outperforming popular methods like Lipofectamine 2000 and FuGENE HD.
  • Key factors for efficient gene delivery were identified, including the length and ratio of hydrophobic alkyl substitutions, leading to better results than conventional cationic PEI and enabling the successful transfer of two plasmid DNAs into challenging human embryonic stem cells for optogenetic research.

Article 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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Source
http://dx.doi.org/10.1016/j.bmc.2024.118008DOI Listing

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