Biodelivery of therapeutic extracellular vesicles: should mononuclear phagocytes always be feared?

At present, extracellular vesicles (EVs) are considered key candidates for cell-free therapies, including treatment of allergic and autoimmune diseases. However, their therapeutic effectiveness, dependent on proper targeting to the desired cells, is significantly limited due reduced bioavailability resulting from rapid clearance by cells mononuclear phagocyte system (MPS). Thus, developing strategies avoid EV elimination essential when applying them in clinical practice. On other hand, malfunctioning MPS contributes various immune-related pathologies. Therapeutic reversal these effects with EVs would be beneficial could achieved, example, modulating macrophage phenotype or regulating antigen presentation dendritic cells. Additionally, intended macrophages replication repackaging molecules into new vesicle subtype can allow specific appropriate populations acceptor Herein, we briefly discuss under-explored aspects MPS-EV interactions that undoubtedly require further research order accelerate use EVs.