Investigation of Cubosome Interactions with Biomimetic Plasma Membranes

Cubosomes are nanostructured lipid particles that have gained significant attention in nanomedicine and drug delivery due to their amphiphilic nature and ability to encapsulate diverse therapeutic agents. This study investigates the biophysical interactions between phytantriol-based cubosomes and biomimetic plasma membranes, modeled as Giant Unilamellar Vesicles (GUVs). 

Cubosomes were synthesized via a top-down approach, utilizing high-energy homogenization of a bulk cubic phase. The resulting nanoparticles were structurally and morphologically characterized using SAXS and DLS. 

The biomimetic GUVs were grown in-vitro using the electroformation technique. To comprehensively analyze the interactions, we first established control parameters by verifying the structural integrity of bare GUVs across different model systems: pure POPC, POPC/cholesterol mixtures, and Rhodamine-labeled POPC. Following this verification, the characterized cubosomes were introduced to the GUVs, and the interaction dynamics were monitored via optical microscopy. 

The results demonstrated significant membrane activity, revealing pronounced topological alterations in the GUVs upon contact with the nanoparticles. Specifically, we observed the induction of budding, vesicle fission, pore formation, and a notable expansion of the superficial area. Furthermore, the onset time required for these topological alterations to begin varied significantly depending on the specific lipid composition of the target GUV. These dynamic and composition-dependent changes highlight the complex nature of cubosome-membrane interactions, providing crucial insights into their mechanisms as delivery vectors.