Combined SANS/SAXS and model-independent simulations for structure determination of complex, therapeutically relevant lipid nanoparticles

Research Project, 2018 – 2021

Lipid nanoparticles (LNPs) have evolved into smart multifunctional carriers for drug delivery most notably in the thriving field of siRNA and mRNA therapeutics. Characterization of LNP bulk and in particular surface structure is of eminent importance to understand their interactions and therapeutic function. The concurrent use of neutron and X-ray scattering in both the small and wide angle regime would provide the necessary information. However, utilizing the full potential of these techniques is today hampered, mainly due to the absence of analytical models for complex partially ordered multi-component systems. To address the challenge of consistent data analysis novel coarse grained computational approached will be developed with the aim to provide a generic multi-experiment analysis tool to a larger community that integrates data of contrast variation series, temperature runs and environmental changes. The necessary data will be obtained by the use of hard (18keV) X-rays and SANS measurement on the same samples, for which the proper measurement cells will be developed. The German-Swedish team consist of complementary competence in SANS and X-ray instrument development and operation, biophysics, lipid self-assembly, therapeutic formulations and computational modelling.