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

Abstract

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.