Synergistic immunomodulatory effect in macrophages mediated by magnetic nanoparticles modified with miRNAs
Nuria Lafuente‐Gómez, Shiqi Wang, Flavia Fontana, Mónica Dhanjani, David García‐Soriano, Alexandra Correia, Milagros Castellanos, Ciro Rodríguez Díaz, Gorka Salas, Hélder A. Santos, Álvaro Somoza
Abstract
In this work, we describe the synthesis of magnetic nanoparticles composed of a maghemite core (MNP) and three different coatings (dextran, D-MNP; carboxymethyldextran, CMD-MNP; and dimercaptosuccinic acid, DMSA-MNP). Their interactions with red blood cells, plasma proteins, and macrophages were also assessed. CMD-MNP was selected for its good biosafety profile and for promoting a pro-inflammatory response in macrophages, which was associated with the nature of the coating. Thus, we proposed a smart miRNA delivery system using CMD-MNP as a carrier for cancer immunotherapy applications. Particularly, we prove that CMD-MNP-miRNA155 and CMD-MNP-miRNA125b nanoparticles can display a pro-inflammatory response in human macrophages by increasing the expression of CD80 and the levels of TNF-α and IL-6. Hence, our proposed miRNA-delivery nanosystem can be exploited as a new immunotherapeutic tool based on magnetic nanoparticles.