Dextran‑coated superparamagnetic iron oxide nanoparticles activate the MAPK pathway in human primary monocyte cells

Abstract

With the increase in applications of superparamagnetic iron oxide nanoparticles (SPIONs) in biomedicine, it is essential to investigate the bio‑security of these nanoparticles, especially with respect to the human immune system. In the present study, the biological effects of dextran‑coated superparamagnetic iron oxide nanoparticles (Dex‑SPIONs) on human primary monocyte cells were evaluated. The results of the present study demonstrated that Dex‑SPIONs can be identified in phagosomes or freed in the cytoplasm and did not affect cell viability or induce apoptosis. Notably, there were certain bulky vacuoles and a number of pseudopodia from the cell membrane, suggesting potential activation of human monocyte cells. In addition, the expression levels of pro‑inflammatory cytokines interleukin (IL)‑1β and tumor necrosis factor (TNF)‑α were also increased following treatment with Dex‑SPIONs. Simultaneously, the phosphorylation levels of mitogen‑activated protein kinase (MAPK) p38, c‑Jun N‑terminal kinase 1 and extracellular signal regulated kinase were markedly enhanced following nanoparticle exposure and MAPK inhibitors could abate the production of IL‑1β and TNF‑α. The results of the present study demonstrated that Dex‑SPIONs could activate human monocyte cells and that activation of MAPK pathway may be involved in these effects.

Nanoparticle Surface Functionalization: How to Improve Biocompatibility and Cellular Internalization

“…The use of dextran with iron-oxide nanoparticles to improve biocompatibility was also studied using primary cells. Wu et al (2018) demonstrated that dextran-NPs had no significant effects on cell viability and apoptosis on human primary monocytes cells.…”

Impact of Superparamagnetic Iron Oxide Nanoparticles on THP-1 Monocytes and Monocyte-Derived Macrophages

“…A SPION-induced activation of monocytes as well as a phenotypic shift of M2-like towards M1-like macrophages have been repeatedly proposed ( Laskar et al, 2013 ; Rojas et al, 2016 ). Another publication proved an activation of MAPK signaling pathways in primary human monocytes that resulted in secretion of pro-inflammatory cytokines ( Wu et al, 2018 ). Sindrilaru and colleagues even suggested an iron-mediated regulation of the functional plasticity of monocytes ( Sindrilaru et al, 2011 ).…”

Application of Nanomedicine in Immunotherapy: Recent Advances and Prospects

“…In general, monocytes or macrophages are able to uptake SPIONs relatively rapidly (few hours) [114,170]. Wu et al demonstrated in primary human monocyte cells that SPI-ONs can be identified in phagosomes or in cytoplasm [171]. However, there are two noteworthy items regarding the cellular uptake of SPIONs: their size and their charge.…”

“…Another important parameter to consider is the impact of SPIONs on cell viability in order to take advantage of the beneficial effects provided by anti-cancer therapies while minimizing the harmful adverse effects potentially induced by SPION vectors, especially since SPIONs cytotoxicity remains unclear [171]. In fact, several variables considerably complicate the evaluation of SPION cytotoxicity.…”