Sucrose ester embedded lipid carrier for DNA delivery

[Display omitted] •A series of NLCs were constructed based on SEs and peptide lipids for DNA delivery.•The COL-6 with sucrose laurate exhibits highest transfection efficiency.•SEs increased the interaction of NLC to DNA, it decreased with the increase of SE carbon chain length.•SEs contributed to the formation of ordered membrane structure and enhanced stability.•The addition of SEs enhances lipid aggregation, and DNA molecules twine around the NLCs or are partially compressed within them. Sucrose esters (SEs) have great potential in the field of nucleic acid delivery due to their unique physical and chemical properties and good biosafety. However, the mechanism of the effect of SEs structure on delivery efficiency has not been studied. The liposomes containing peptide lipids and SEs were constructed, and the effects of SEs on the interaction between the liposomes and DNA were studied. The addition of SEs affects the binding rate of liposomes to DNA, and the binding rate gradually decreases with the increase of SEs’ carbon chain length. SEs also affect the binding site and affinity of liposomes to DNA, promoting the aggregation of lipids to form liposomes, where DNA wraps around or compresses inside the liposomes, allowing it to compress DNA without damaging the DNA structure. COL-6, which is composed of sucrose laurate, exhibits the optimal affinity for DNA, and SE promotes the formation of ordered membrane structure and enhances membrane stability, so that COL-6 exhibits a balance between rigidity and flexibility, and thus exhibits the highest delivery efficiency of DNA among these formulations. This work provides theoretical foundations for the application of SE in gene delivery and guides for the rational design of delivery systems.