The nanoparticles could be used for delivering medicines to cells and for gene-based cancer therapies, so understanding how they interact with cell membranes is vital for the design of effective new therapeutics.
Lipid nanoparticles have been used to deliver medicines before; the mRNA vaccine for Covid-19 uses liposomes – small, spherical lipid nanoparticles – to deliver the vaccine to cells. However, researchers can create more complex nanoparticles such as cubosomes and hexosomes, and tune their properties. Cubosomes possess a 3D lipid bilayer containing two continuous but unconnected water channels, and hexosomes consist of cylindrical water channels through 2D hexagonal arrays.
The structure of these nanoparticles affects how they interact with cell membranes, which in turn affects how their contents are taken up by cells. The research team used neutron reflectometry to explore how supported lipid bilayers, which mimic a cell membrane, were affected by cubosomes and hexosomes.
For the study, they used glycerol monooleate (GMO) cubosomes and dioleoylphosphatidylethanolamine (DOPE) hexosomes, together with a supported lipid bilayer with and without cholesterol, which plays a role in membrane fluidity and in regulating uptake by cell membranes. The team took measurements on the OFFSPEC instrument at ISIS over several hours, starting five minutes after they introduced the nanoparticles and repeated every twenty minutes, finishing with a final measurement once the system reached equilibrium.
They found that the cubosome and hexosome interacted very differently with the membrane (see image). The results showed that the cubosomes form transient structures on the membrane while exchanging lipids and gradually destabilising it, until the membrane is removed. The study was the first time anybody has reported the kinetics of the interaction between DOPE hexosomes and a model bilayer. They found the hexosomes fused with the bilayer and gradually became part of it. Cholesterol slowed down the effects significantly. Both results were confirmed by atomic force microscopy.
Related publication: https://doi.org/10.1002/admi.202500186
