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

Automated summary

Currently, extracellular vesicles (EVs) are considered promising for cell-free therapies, but their effectiveness is limited by rapid clearance by the mononuclear phagocyte system (MPS). Strategies to avoid EV elimination are necessary for their clinical application. On the other hand, dysfunctional MPS is associated with immune-related pathologies, which could potentially be reversed by EVs through modulating macrophage phenotype or regulating antigen presentation by dendritic cells. Targeting EVs to MPS macrophages for replication and repackaging of their molecules into new vesicle subtype can enable specific targeting to desired cells. Further research on MPS-EV interactions is needed for the therapeutic use of EVs.