The potential of small extracellular vesicles for pancreatic cancer therapy

Abstract

Extracellular vesicles come in various shapes and sizes and are released by most cell types. They have myriad roles in intercellular signalling in both physiological and pathological environments, carrying a range of lipids, proteins and nucleic acids. Their cargo is then unloaded at the target site inducing a change in their target cell. Cancers use these vesicles to their advantage for a wide range of outcomes such as immune evasion and chemoresistance leading to the reduced effect of chemotherapies and unfavourable patient outcomes. Pancreatic cancer has one of the worst outcomes of any cancer with surgery being the only cure. As surgery is only available in a small number of cases, targeted delivery of cargos directly to the tumour site is of high importance to efficiently target and destroy cancer cells with high effectiveness without the toxic off-target effects of chemotherapy drugs. Hijacking the body's postal system has gained interest in the last decade for the delivery of therapeutic drugs. The low immunogenicity and inherent biocompatibility of extracellular vesicles avoids the hurdles experienced by other nanoparticles such as toxicity. Various techniques for loading and functionalising extracellular vesicles have progressed to clinical trials, however, these therapies are yet to make it onto the market. This review seeks to be a call to action to the pancreatic cancer community, highlighting the potential of these biologic systems in the improvement of therapeutic outcomes of what is one of the deadliest cancers.