(240e) Cell Membrane-Derived, Core-Shell Structures for the Delivery of Biologics

Vesicles loaded with nanoparticles have found increasing applications for the delivery of biologics. However, issues with stability complicate their synthesis and make it difficult to incorporate proteins in vesicles to guide delivery and biological response. Giant plasma-membrane derived vesicles (GPMVs) are membrane vesiculations that are enriched in membrane proteins. Since GPMVs contain cytoplasmic content, loading cells with nanoparticles prior to GPMV induction can provide a novel approach for the synthesis of nanoparticle-loaded vesicles. Herein, we report the generation of such GPMV-based, core-shell structures for the first time and characterize their composition, physicochemical properties, and cellular interactions.

The cell-derived system used in this study was produced from the A549 alveolar epithelial cells. Cells were first pre-incubated with fluorescent carboxyl-modified silica nanoparticles (50 nm) for six hours, resulting in nanoparticle internalization, and then chemically induced for GPMV generation. Isolated vesicles had a diameter of 5.7 ± 2.3 μm and a zeta potential of -9.9 ± 0.6 mV. Confocal imaging confirmed the presence of nanoparticles inside the vesicles. Vesicles showed the same lipid and protein profile as reported for the cell plasma membrane with only minor changes in their proteome after nanoparticle encapsulation. Stability of GPMVs at 37 °C was examined by monitoring the release of the fluorescent nanoparticles, demonstrating that vesicles remained intact for approximately 48 hours. Nanoparticle-loaded GPMVs were readily endocytosed in two different cell lines (A549 and THP1). In summary, this work reports the generation of the first GPMV-based, core-shell, nanoparticle-vesicle structures. These structures, which contain membrane proteins, are simple to generate, stable, and readily endocytosed by cells, and could find applications in delivery of drugs and imaging agents.