Exploring Rapid Lipid Membrane Fusion with Fibroin Nanoparticles within Extracellular Vesicles: A Millisecond Kinetics Investigation Trigger

The project aim is to reveal the mechanism of lipid membrane interaction with fibroin nanoparticles encapsulated into liposomes or extracellular vesicles to design smart systems for delivery of a cytotoxic drug to mesothelloma cells. We developed a novel multicompartment delivery systems, in which cytotoxic drug is encapsulated into fibroin nanoparticles with outer lipid shell. To improve tagreting and transport properties of the nanovectors, the lipid shell was modified by extracelluar vesicles. However, the internal structure of such hybrid nanovectors remains unknow as well as fusion mechanism with lipid membranes and effect of protein corona on their interaction, that is crucial to optimize shell composition for efficient drug delivery and release. We will study the arrangement of fibroin in the lipid nanoparticles and lipids in hybrid shell by SAXS/WAXS, while mechanism of fusion with membrane will be revealed by time-resolved experiment in millisecond timescale.