Engineering Liposomes with Cell Membrane Proteins to Disrupt Melanosome Transfer between Cells

Cells
communicate by transporting vesicles and organelles,
which
is essential for maintaining cellular homeostasis. However, dysregulated
vesicle transfer between cells can contribute to several diseases.
In the skin, excessive melanosome transfer from melanocytes to keratinocytes
leads to hyperpigmentation and can contribute to the progression of
melanoma. Current treatments often rely on eliminating the contents
of melanosomes with drugs, which risks significant side effects. Here,
we present a drug-free strategy to regulate intercellular transport.
We demonstrate our approach by reducing the amount of melanosomes
transferred from melanocytes to keratinocytes. To achieve this, we
incorporate keratinocyte cell membrane proteins into liposomes formed
with microfluidics. Such functionalization enables the liposomes to
selectively anchor to the surface of pigment globules, which transport
melanosomes between cells. We show that the liposomes passivate the
pigment globule surface and inhibit their uptake by keratinocytes,
which results in a significant reduction in the level of melanosome
transfer. Thus, our findings provide an effective strategy for reducing
melanosome transfer and present a generalizable method for modulating
cellular communication through extracellular vesicles and organelles.