Programming Cell-Derived Vesicles with Enhanced Immunomodulatory Properties.

ABSTRACT

Tumor-associated macrophages are the predominant immune cells present in the tumor microenvironment and mostly exhibit a pro-tumoral M2-like phenotype. However, macrophage biology is reversible allowing them to acquire an anti-tumoral M1-like phenotype in response to external stimuli. A potential therapeutic strategy for treating cancer may be achieved by modulating macrophages from an M2 to an M1-like phenotype with the tumor microenvironment. Here, programmed nanovesicles are generated as an immunomodulatory therapeutic platform with the capability to re-polarize M2 macrophages toward a proinflammatory phenotype. Programmed nanovesicles are engineered from cellular membranes to have specific immunomodulatory properties including the capability to bidirectionally modulate immune cell polarization. These programmed nanovesicles decorated with specific membrane-bound ligands can be targeted toward specific cell types including immune cells. Macrophage-derived vesicles are engineered to enhance immune cell reprogramming toward a proinflammatory phenotype.