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 Rodriguez Diaz; Gorka Salas; Hélder A. Santos; Álvaro Somoza

doi:10.1039/D2NR01767A

Synergistic immunomodulatory effect in macrophages mediated by magnetic nanoparticles modified with miRNAs†

Nuria Lafuente-Gómez,

*^a Shiqi Wang,

^b Flavia Fontana,^b Mónica Dhanjani,^a David García-Soriano,^a Alexandra Correia,^b Milagros Castellanos,^a Ciro Rodriguez Diaz,

^a Gorka Salas,

^ac Hélder A. Santos

*^bd and Álvaro Somoza

*^ac

Author affiliations

* Corresponding authors

^a Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Madrid, Spain
E-mail: nuria.lafuente@imdea.org, alvaro.somoza@imdea.org

^b Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland

^c Unidad de Nanobiotecnología Asociada al Centro Nacional de Biotecnología (CSIC), Madrid, Spain

^d Department of Biomedical Engineering, W.J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen/University of Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands
E-mail: h.a.santos@umcg.nl

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.

Nanoscale

Synergistic immunomodulatory effect in macrophages mediated by magnetic nanoparticles modified with miRNAs†

Abstract

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Synergistic immunomodulatory effect in macrophages mediated by magnetic nanoparticles modified with miRNAs

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