Influence of Lipid Thioether Modification and Formulation Method on Lipoplex Structure, Stability and Transfection Efficiency in HEK293T Cells
M. Rochedy, L. Dechamboux, A. Dupont, M. Berchel, P.A. Jaffrès, J.P. Chapel, T. Vivès, P. Leroyer, S. Tranchimand, F. Gauffre, F. Nallet, C. Schatz, P. Loyer, L.M. Bravo Anaya
J. Mater. Chem. B, 2026, ASAP, DOI: 10.1039/D6TB00356G
Published 31 August 2026
 

The efficacy of lipoplexes (cationic lipids/pDNA complexes) depends on their lipid structure and the formulation method. This study compares two structurally similar cationic lipids, BSV107-S and BSV107, which differ only in their hydrophobic chains. Both lipids were formulated with peGFP-C3 plasmid using either “bulk” complexation with preformed liposomes or “one-step” microfluidic assembly. Both approaches resulted in the formation of nanocomplexes, with the formulations prepared by microfluidic devices exhibiting smaller sizes. Cryo-TEM and SAXS analyses revealed a multilamellar organisation, which was particularly widely spaced in BSV107-S-based lipoplexes prepared using microfluidic devices. Transfection efficiency in HEK293T cells shows that BSV107-S consistently exhibits higher efficiency than BSV107, regardless of the formulation method. These higher efficiencies are associated with increased membrane fluidity, highlighting 'structure-formulation-property' relationships that are useful for designing new non-viral gene vehicles.