Galactomannan-graft-poly(methyl methacrylate) nanoparticles induce an anti-inflammatory phenotype in human macrophages

Abstract

Macrophages are immune cells that can be activated into either pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Attempts to modulate macrophage phenotype using drugs have been limited by targeting issues and systemic toxicity. This study investigates the effect of drug-free self-assembled hydrolyzed galactomannan-poly(methyl methacrylate) (hGM-g-PMMA) nanoparticles on the activation of the human monocyte-derived macrophage THP-1 cell line. Nanoparticles are cell compatible and are taken up by macrophages. RNA-sequencing analysis of cells exposed to NPs reveal the upregulation of seven metallothionein genes. Additionally, the secretion of pro-inflammatory and anti-inflammatory cytokines upon exposure of unpolarized macrophages and M1-like cells obtained by activation with lipopolysaccharide + interferon-γ to the NPs is reduced and increased, respectively. Finally, nanoparticle-treated macrophages promote fibroblast migration in vitro. Overall, results demonstrate that hGM-g-PMMA nanoparticles induce the release of anti-inflammatory cytokines by THP-1 macrophages, which could pave the way for their application in the therapy of different inflammatory conditions, especially by local delivery.