Modelling of the Interaction between Cationic Lipid Dlin-Kc2-Dma (XTC2) and Anionic Lipid Distearoylphosphatidylserine (DSPS)

Abstract

Short pieces of double stranded small interfering RNA (siRNA) could be used as a potential drug to cure cancer by binding to cancer gene's messenger RNA. However, the siRNA is not stable in the blood stream, and tends not to penetrate target cell membrane. So, it must be encapsulated in a lipid nanoparticle. LNPs have been shown to be strong candidates for drug delivery [1]. Lipid nanoparticles (LNPs) are a new tool for drug delivery systems. They are responsible for transferring short pieces of double stranded small interfering RNA (siRNA) into the cell. However, the underlying mechanism of action of lipid constituents of LNPs is not clearly known. Specifically, characteristics such as encapsulation efficiency, and the stability of LNPs are not predictable. Cationic lipids play essential roles in encapsulating negatively charged siRNA and also destabilizing the endosomal membrane. We have studied the bilayer and inverted hexagonal phase (HII) phase stability as it could potentially show the destabilizing effect of LNPs on the endosomal membrane for DLin-KC2-DMA (XTC2) at different temperatures. It has shown good destabilizing effects for bilayer structures. We also studied the interaction of the distearoylphosphatidylserine (DSPS) with XTC2 based on comparison with deuterium order parameters obtained from NMR experiments since DSPS has been used to optimize the structure of XTC2 [1]. pH, water content, temperature, and salt concentration effects on the bilayer HII phase stability is also studied.[1] S. de Youg, G. C. Chikh, L. L. Sekirov, S. Raney, S. C. Semple, S. K. Klimuk, Z. N. Yuan, M. Hope, P. R. Cullis, Y. K. Tam, Cancer Immunology and Immunotherapy, 56, 1251-1264, 2007.