Theranostic Iron Oxide Nanoparticle Cargo Defines Extracellular Vesicle‐Dependent Modulation of Macrophage Activation and Migratory Behavior

• Published in: Advanced biosystems Vol. 2; no. 9
• Main Authors: Mulens‐Arias, Vladimir, Nicolás‐Boluda, Alba, Silva, Amanda K Andriola, Gazeau, Florence
• Format: Journal Article
• Language: English
• Published: 01-09-2018
• Subjects: endothelial cells; macrophages; mesenchymal stem cells; podosome; SPION
• ISSN: 2366-7478; 2366-7478
• DOI: 10.1002/adbi.201800079

Cells shed submicronic extracellular vesicles (EVs), containing a variety of soluble and membrane‐embedded factors, to mediate intercellular communication. EVs show differential immunomodulatory features depending on the cell source and physiological status, endowing these nanosystems with intrinsic immunotherapeutic potential. EVs could be used to mount a potent immune response against tumor cells, by regulating inflammatory cues in tumors and modulating macrophage activation and migratory behavior. On the other part, EVs are loaded with theranostic nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs), to confer them magnetic detection, manipulation, and heating capabilities. However, little is known about the impact that SPION may have on intrinsic immunomodulatory properties of EVs. Here, the effects are characterized on the activation and dynamics of macrophages induced by EVs derived from mouse mesenchymal stem cells and mouse/human endothelial cells, loaded or not with SPION. EVs differently activate macrophages as determined by cytokine secretion, phagocytosis capacity, migratory behavior, and extracellular matrix degradation capacity. SPION loading prove to amplify the immunoregulatory properties of EVs, increasing the macrophage ability to migrate, and degrade extracellular matrix. Altogether, EVs might potentiate natural or induced immune response by modulating macrophage activation/migratory behavior, suggesting their use as nanocarriers in combinatorial therapeutic approaches with SPION.
Extracellular vesicles (EVs) possess promising targeting properties and can modulate immune response. Inorganic nanoparticles can be loaded into EVs; however, little is known about how the cargo might modulate intrinsic EV bioactivities. Here, it is demonstrated how superparamagnetic iron oxide nanoparticles cargo change EV‐triggered macrophage activation and podosome/rosette dynamics.