Cell-derived Giant Membrane Vesicles Enclosing the Anthracycline Anti-Cancer Drug Doxorubicin and their Cytotoxicity

Abstract: Although giant membrane vesicles prepared from paraformaldehyde-treated mammalian cells have been used to elucidate lipid and protein dynamics on the cell surface, there are few studies that have used them as a tool to deliver drugs to cells. Here we found that anti-cancer drug doxorubicin (Dox) was efficiently incorporated into and stably retained in giant membrane vesicles prepared from HeLa human cervical cancer cells. Intriguingly, coincubation of Dox-enclosed giant membrane vesicles with human pancreatic cancer-derived PK-59 and gastric cancer-derived KE-39 cells led to cell death. Microscopic observation of vesicle-docked cells revealed that docking of at least one to a few Dox-enclosed giant vesicles on the cellular cortex was sufficient to induce cell death, suggesting applicability of cell-derived giant membrane vesicles as an efficient drug delivery vector in cultured cell systems. Keywords: Anti-cancer treatment, Extracellular vesicle, Doxorubicin, Drug delivery