Evaluation of Maltose-Based Cationic Liposomes with Different Hydrophobic Tails for Plasmid DNA Delivery

In this paper, three cationic glycolipids with different hydrophobic chains Malt-DiC12MA (IX a), Malt-DiC14MA (IX b) and Malt-DiC16MA (IX c) were constructed by using maltose as starting material via peracetylation, selective 1-O-deacetylation, trichloroacetimidation, glycosylation, azidation, deacetylation, Staudinger reaction, tertiary amination and quaternization. Target compounds and some intermediates were characterized by (1)H-NMR, (13)C-NMR, (1)H-(1)H COSY and (1)H-(13)C HSQC. The results of gel electrophoresis assay, atomic force microscopy images (AFM) and dynamic light scattering (DLS) demonstrate that all the liposomes could efficiently bind and compact DNA (N/P ratio less than 2) into nanoparticles with proper size (88 nm–146 nm, PDI < 0.4) and zeta potential (+15 mV–+26 mV). The transfection efficiency and cellular uptake of glycolipids in HEK293 cell were evaluated through the enhanced green fluorescent protein (EGFP) expression and Cy3-labeled pEGFP-C1 (Enhanced Green Fluorescent Protein plasmid) images, respectively. Importantly, it indicated that Malt-DiC14MA exhibited high gene transfer efficiency and better uptake capability at N/P ratios of 8:1. Additionally, the result of cell viability showed glycolipids exhibited low biotoxicity and good biocompatibility by thiazolyl blue tetrazolium bromide (MTT) assay.