Structural features of glutamate-based lipidic materials for small interfering RNA delivery system

Understanding of materials for small interfering RNA (siRNA) delivery system is essential for the effective design and selection of appropriate materials as potential applications in basic and therapeutic research. However, little attempt has been made to investigate how the structural features of lipidic materials are essential for delivery function. The purpose of this study was to identify the structural features of glutamate-based lipidic materials as potential siRNA carriers for intracellular delivery. Totally designed lipid didodecylacetylglutamatetrimethylammonium (TMA-C2-Glu-C12) and its analogs were synthesized and estimated by silencing effects of fluorescent protein (EGFP) expression in CHO-EGFP cells. Here, we demonstrate that TMA-C2-Glu-C12 among a series of lipidic materials is able to perform efficient siRNA delivery with low cytotoxicity into the cells; the transfer ability resulted in 92.2% +/- 1.16% of the transferred cells with Cy3-labeled siRNA. The chemical structure of TMA-C2-Glu-C12 having both hydrophobic chain (--CH(2)CO--) in head region, hydrophobic chain (--(CH(2))(11)CH(3)) in tail regions, and ethylene (--CH(2) CH(2)--) in connector region played a crucial role to enhance the siRNA transfer efficiency. Moreover, compared with commercial reagents, TMA-C2-Glu-C12 was found to have an effective activity for siRNA delivery. These results may improve the novel design and development of lipidic materials on siRNA delivery system.