Cell membrane-derived vesicles for cancer targeting

Extracellular vesicles (EVs) are emerging as interesting theranostic tools, presenting features that make them feasible drug delivery systems. However, the application of EVs in drug delivery is hampered by several issues like the high heterogeneity and batch-to-batch variation caused by the lack of efficient GMP protocols, possible contamination due to residual genetic material, difficulty in drug loading, low production and isolation yield hindering scalability [1,2]. It was already reported in the literature that cell-deriving nanosystems, composed of cancer cell membranes, either neat or fused with artificial liposomes, have selective homologous targeting abilities [3]. The purpose of our project is to develop a safe biomimetic nanosystem able to target parent malignant tumor cells, exploiting its cancer-mimetic characteristics. To this aim, selected glioblastoma cell homogenates underwent a differential centrifugation procedure, allowing the isolation of cell membrane fragments, which were extruded through polycarbonate filters to yield nanovesicles; the vesicles were characterized for their chemical-physical and morphological properties by photon-correlation spectroscopy and transmission electron microscopy (TEM) (Fig. 1). Future studies will be performed to confirm the presence of membrane proteins typical of the parent cancer cells on the vesicle surface, being these markers fundamental for targeting. Moreover, to improve the scalability of the system, the possibility of developing hybrid vesicles, obtained by fusion with liposomes, will be evaluated.