Macrophage endocytosis of superparamagnetic iron oxide nanoparticles - Mechanisms and comparison of Ferumoxides and Ferumoxtran-10
Macrophage endocytosis of superparamagnetic iron oxide nanoparticles - Mechanisms and comparison of Ferumoxides and Ferumoxtran-10
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DOI：
10.1097/01.rli.0000101027.57021.28
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发表时间：
2004-01-01
影响因子：
6.7
通讯作者：
Corot, C
中科院分区：
文献类型：
--
作者：
Raynal, I;Prigent, P;Corot, C
原理和目的：用作磁共振（MR）造影剂的超顺磁性氧化铁（SPIO）会被巨噬细胞特异性摄取。本研究的目的首先是通过与清道夫受体SR-A（I/II）特异性配体的竞争实验确定Ferumoxides的巨噬细胞摄取机制，其次是评价和比较2种不同造影剂Ferumoxides（SPIO）和Ferumoxtran-10的内化（USPIO：超小型超顺磁性氧化铁），使用通过化学活化人单核细胞获得的巨噬细胞。Ferumoxides和Ferumoxtran-10是2种MR造影剂，由葡聚糖涂层氧化铁纳米颗粒组成。在清道夫受体SR-A（I型和II型）的特异性配体：聚肌苷酸和岩藻依聚糖存在下，使用小鼠腹腔巨噬细胞的竞争实验研究了Ferumoxides的内吞途径。在存在2种超顺磁性纳米颗粒的情况下，使用活化成巨噬细胞的THP-1（人前单核细胞）细胞进行体外测定。用ICP-AES（电感耦合等离子体-原子发射光谱法）和普鲁士蓝染色法测定铁含量。结果：多聚肌苷酸和岩藻依聚糖硫酸酯均能抑制小鼠腹腔巨噬细胞对铁的内吞作用。使用浓度为62.5 μ g Fe/mL SPIO的10 μ g/mL清道夫受体配体获得这种抑制，并观察到剂量依赖关系。在没有竞争对手的情况下，小鼠腹腔巨噬细胞对Ferumoxides的摄取百分比范围为3%至8%。在人活化单核细胞THP-1细胞试验中，Ferumoxides的巨噬细胞摄取（1.1%-3%）高于Ferumoxtran-10（0.03%-0.12%）。结论：竞争实验表明，Ferumoxides的细胞摄取涉及清道夫受体SR-A介导的内吞作用。Ferumoxides和Ferumoxtran-10之间的比较证实，巨噬细胞对氧化铁纳米颗粒的摄取主要取决于这些造影剂的大小。
Rationale and objectives: Superparamagnetic iron oxides (SPIO) used as magnetic resonance (MR) contrast agents undergo specific uptake by macrophages. The purpose of this study was first to determine the mechanism of macrophage uptake for Ferumoxides by using competition experiments with specific ligands of scavenger receptors SR-A (I/II) and second, to evaluate and compare the internalization of 2 different contrast agents, Ferumoxides (SPIO) and Ferumoxtran-10 (USPIO: ultrasmall superparamagnetic iron oxide) using macrophages obtained by chemical activation of human monocytic cells.Methods: Ferumoxides and Ferumoxtran-10 are 2 MR contrast agents, composed of dextran-coated iron oxide nanoparticles. The endocytosis pathway of Ferumoxides was studied using competition experiments on mouse peritoneal macrophages in the presence of specific ligands of scavenger receptors SR-A (types I and II): polyinosinic acid and fucoidan. In vitro assays using THP-1 (human promonocyte) cells activated into macrophages were performed in the presence of the 2 superparamagnetic nanoparticles. The cellular uptake was determined by measuring the iron content using ICP-AES (inductively coupled plasma-atomic emission spectrometry) and by Prussian blue staining.Results: In the presence of polyinosinic acid or fucoidan, the endocytosis of Ferumoxides by mouse peritoneal macrophages was inhibited. This inhibition was obtained using 10 mug/mL of scavenger receptor ligands at a concentration of 62.5 mug Fe/mL of SPIO, and a dose-dependent relationship was observed. Without competitors, the percentage of uptake of Ferumoxides by mouse peritoneal macrophages ranged between 3 and 8%. On the human activated monocyte THP-1 cell assay, Ferumoxides underwent a higher macrophage uptake (between 1.1 and 3%) compared with Ferumoxtran-10 (between 0.03 and 0.12%). This difference is attributed to the larger size of Ferumoxides nanoparticles.Conclusions: Competition experiments indicate that the cellular uptake of Ferumoxides involves scavenger receptor SR-A-mediated endocytosis. The comparison between Ferumoxides and Ferumoxtran-10 confirms that macrophage uptake of iron oxide nanoparticles depends mainly on the size of these contrast agents.