Metabolism and Biodistribution of Modified Extracellular Vesicles in Colorectal Cancer Models

Abstract

Exosomes are one of the types of extracellular vesicles (EVs) that are nanosized membranous vesicles that are secreted from the multivesicular bodies. Tumor derived EVs (TEVs) negatively regulate the immunity in Colorectal Cancer (CRC). Previous research in our lab has established that modified EVs generated by blocking microRNA424/322 (miR424/322) in TEVs ,enhanced the CD28-CD80/86 co-stimulatory pathway in T cells and dendritic cells which further increased the anti-tumor response in CRC mouse model. Recently, EVs have been identified to regulate the metabolism in CRC. Our data suggests that knocking down miR424 in CRC cells alters their metabolic machinery. Moving forward, one of the critical aspects of using EVs as a therapy or drug delivery system is to determine their biodistribution in-vivo. Our data demonstrated that modified EVs show predominant biodistribution in liver, lung and spleen. These findings shall help in developing novel therapeutic strategies for curing CRC.