丁香园AV

Synopsis

Lipid Nanoparticles (LNPs) are an attractive way of delivering of short interfering RNA (siRNA) for cancer therapeutics. Their release method relies on protonation the ionisable amino-lipid XTC2 in acidic endosomes. Hypothetically, the protonated XTC2 and anionic lipids in endosomal membranes interact to form non-lamellar phases, releasing the siRNA. In this project a model release system consisting of XTC2 and anionic distearoyl-phosphatidylserine (DSPS-d70) at pH 4.7 was investigated with deuterium nuclear magnetic resonance (²H NMR) and small angle x-ray scattering (SAXS) to determine the lipid phases which form as a function of temperature and their structural parameters. Since cholesterol is an important structural component in LNPs, increasing amounts of cholesterol were added to the system to determine its effect. Non-lamellar phases were observed for each sample particularly at high temperatures, though interestingly the specific phase observed by each technique was not always in complete agreement.

Keywords: Lipid Nanoparticles; Phosphatidylserine; Cholesterol; Small Angle X-Ray Scattering; Deuterium Nuclear Magnetic Resonance