Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro

被引:0
作者
Multi-Imaging Centre, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, United Kingdom [1 ]
不详 [2 ]
不详 [3 ]
不详 [4 ]
不详 [5 ]
不详 [6 ]
机构
[1] Multi-Imaging Centre, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3DY, Downing Street
[2] Department of Earth and Environmental Sciences, Pannon University, Veszprém, H-8200
[3] Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Cambridge
[4] Direction Recherche, Guerbet, 95943 Roissy CDG Cedex
[5] Neurology Biomarkers, Translational Medicine and Genetics, GlaxoSmithKline, Cambridge
[6] Clinical Imaging Applications, Translational Medicine and Genetics, GlaxoSmithKline, Greenford
基金
英国惠康基金;
关键词
Cell activation; Cytotoxicity; Electron microscopy; Inflammation; Macrophage; Nanoparticle;
D O I
10.1016/j.biomaterials.2006.12.003
中图分类号
学科分类号
摘要
Ferumoxtran-10, a dextran-coated ultrasmall superparamagnetic iron oxide particle, has the potential to reveal macrophages in vivo using magnetic resonance imaging potentially acting as a marker of inflammatory status. Pending clinical trials, we examined the interactions of Ferumoxtran-10 with human monocyte-macrophages (HMMs) in vitro to assess its safety and lack of pro-inflammatory activity. After 72 h, Ferumoxtran-10 was not toxic at 1 mg/ml and may be only mildly toxic at 10 mg/ml. Viability in cells with a high intracellular Ferumoxtran-10 load was not affected over 14 days. Ferumoxtran-10 did not interfere with baseline or stimulated cytokine (interleukin-12, interleukin-6, tumour necrosis factor-α or interleukin-1β) or superoxide anion production or with Fc-receptor-mediated phagocytosis. Similarly, Ferumoxtran-10 did not induce cytokine production and was not chemotactic. High-resolution electron microscopy and selected-area electron diffraction confirmed the core of Ferumoxtran-10 is composed of crystalline magnetite. Bright field transmission electron microscopy of thin sections demonstrated that Ferumoxtran-10 was retained in lysosomes of HMM for several days. Ferumoxtran-10 is not toxic to HMMs in vitro, does not activate them to produce pro-inflammatory cytokines or superoxide anions, is not chemotactic and does not interfere with Fc-receptor-mediated phagocytosis. Furthermore, extremely high intracellular Ferumoxtran-10 concentrations had only slight or no effects on these key activities. © 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1629 / 1642
页数:13
相关论文
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