Neutron Reflectivity Study of Extrcellular Vesicles fusion with Lipid Membrane

The goal of the proposal is to perform neutron reflectivity experiment to study the mechanism of lipid membrane fusion with fibroin nanoparticles encapsulated into extracellular vesicles for designing systems for delivery of anticancer drugs to mesothelloma cells. We developed a novel multicompartment delivery systems, in which cytotoxic drug is encapsulated into fibroin nanoparticles with outer lipid shell. The lipid shell was modified by extracelluar vesicles in order to improve tagreting and transport properties of the nanovectors. However, the mechanism of fusion, the arrangement of the lipids in the membrane after fusion, and the effect of protein corona on fusion remain unclear, that is crucial to optimize shell composition for efficient drug delivery and release. We will study the arrangement of the lipids and proteins in the membrane after fusion of extracellular vesicles with encapsulated silk fibroin nanoparticles and model lipid membrane by neutron reflectivity with contrast variation using deuterated and protonated lipids and by varying H2O-to-D2O ratio.