Tumor-derived extracellular vesicles hybridized liposomes in cancer therapy.

Abstract

Extracellular vesicles (EVs) have gained widespread interest due to their potential in the treatment of inflammation, autoimmune diseases, and immuno-cancer therapy. Among various classes of EVs such as microvesicles (MVs), exosomes, and apoptotic bodies, exosomes are of endosomal origin that are released into the extracellular environment. Exosomes carry complex sets of cargo from their cells of origin, including proteins, lipids, mRNA, and DNA, hence exhibit “Mother Nature”. These are typically 30-150 nm lipidic vesicles rich in integrin proteins that facilitate intrinsic cellular targeting. Within the background, we hypothesized that when these exosomes are hybridized with synthetic liposomes, it would help navigate the hybrid construct in the complex biological environment to find its target. Toward this endeavor, we have re-engineered a synthetic liposome with the exosomes (herein called LEVs) derived from mouse breast cancer and incorporated a fluorescent dye to investigate its potential for cellular targeting. Using the membrane extrusion, we have successfully hybridized both entities resulting in the formation of LEVs and characterized for their colloidal properties and stability over a period. LEVs were monodispersed with an average hydrodynamic size of 120±6. Using Elisa and western-blot, we monitored and quantified exosome-specific protein CD63, which was taken as a handle to ensure the reproducibility of exosome and LEVs. These LEVs were rapidly taken up by immune cells and their parent cells thereby confirming their targeting properties, which can be exploited in drug delivery applications. We will discuss biomedical applications such as its distribution in an animal model, biocompatibility, and imaging in this presentation. We anticipate that this study can picture future opportunities for drug delivery solutions that are superior in target recognition.