Superparamagnetic iron oxide nanoparticle uptake alters M2 macrophage phenotype, iron metabolism, migration and invasion

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• 作者：José ; M. Rojas ; PhD^a ; ¹ ; ^{jmrojas@cnb.csic.es" class="auth_mail" title="E-mail the corresponding author} ; Laura Sanz-Ortega ; MSc^a ; ¹ ; Vladimir Mulens-Arias ; PhD^a ; Lucí ; a Gutié ; rrez ; PhD^b ; Sonia Pé ; rez-Yagü ; e ; BSc^a ; Domingo F. Barber ; PhD^a ; ^{dfbarber@cnb.csic.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AD ; Aminodextran ; APS ; 3-aminopropyl-triethoxysilane ; BMM ; Bone marrow-derived macrophages ; BMM-M2 ; Bone marrow-derived macrophages polarised to M2 ; DMSA ; Dimercaptosuccinic acid ; DMT-1 ; Divalent metal transporter-1 ; ERK ; Extracellular signal-regulated kinase ; FPN-1 ; Ferroportin-1 ; IFN ; Interferon ; IL ; Interleukin ; IRE ; Iron response element ; IRP ; Iron-responsive element-binding proteins ; JNK ; c-Jun N-terminal kinase ; LPS ; Lipopolysaccharide ; MAPK ; Mitogen-activated protein kinase ; MFI ; Mean flu
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：12
• 期：4
• 页码：1127-1138
• 全文大小：2070 K

文摘

Superparamagnetic iron oxide nanoparticles (SPIONs) have shown promise as contrast agents and nanocarriers for drug delivery. Their impact on M2-polarised macrophages has nonetheless not been well studied. Here we explored the effects of SPIONs coated with dimercaptosuccinic acid, aminopropyl silane or aminodextran in two M2 macrophage models (murine primary IL-4-activated bone marrow-derived macrophages and human M2-like differentiated THP-1 cells). All SPIONs were internalised and no cell toxicity was observed. SPION treatment produced reactive oxygen species and activated the extracellular signal-regulated kinase and AKT pathways. After 24-h SPION incubation, M2 macrophages switched their iron metabolism towards an iron-replete state. SPION treatment in both M2 macrophage models altered their M2 activation profiles, promoted IL-10 production, and stimulated protease-dependent invasion. These results highlight the need to evaluate the interactions between SPIONs and cells to take full advantage of the intrinsic properties of these nanoparticles in biological systems.

From the Clinical Editor

1000">Superparamagnetic iron oxide nanoparticles (SPIONs) have been used as an MRI contrast agent in many experimental studies. The authors here investigated the effects of these nanoparticles on M2 macrophages after cellular uptake. The findings of cell activation further enhanced our current knowledge on the interaction of SPIONS with macrophages.