Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells

Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells
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DOI:
10.1016/j.biomaterials.2008.05.015
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发表时间:
2008-09-01
期刊:
影响因子:
14
通讯作者:
Tsourkas, Andrew
Tsourkas, Andrew
中科院分区:
工程技术1区
文献类型:
--
作者:
Thorek, Daniel L. J.;Tsourkas, Andrew

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对比增强磁共振(MR)成像的一个有前途的新方向是跟踪体内超顺磁性氧化铁(SPIO)标记细胞的迁移和生物分布。尽管大量的细胞标记的研究已经进行了不同大小和表面电荷的SPIO颗粒,它仍然不清楚SPIO配置提供了最佳的对比度在非吞噬细胞。这在很大程度上是因为矛盾的发现源于表面电荷的可变性和不精确控制,转染和/或靶向剂的一般需求和复杂性,以及在任何给定研究中检查的颗粒构型的有限数量。在本研究中,我们系统地评估了SPIO在非吞噬性T细胞中的细胞摄取,其粒径范围从33 nm到近1.5 μ m,具有精确控制的表面性质,并且不需要转染剂。流式细胞术分析SPIO标记的T细胞,弛豫法测定对比增强。SPIO摄取是剂量依赖性的,并表现出S形电荷依赖性,这表明在不同水平的官能化饱和。对于高达300 nm的颗粒观察到细胞的有效标记,然而,微米级颗粒的摄取是有限的。我们的结果表明,在107 nm处的非常规高度阳离子颗粒配置使T细胞的MR对比度最大化,优于广泛使用的USPIO(< 50 nm)。(c)2008爱思唯尔有限公司保留所有权利。
A promising new direction for contrast-enhanced magnetic resonance (MR) imaging involves tracking the migration and biodistribution of superparamagnetic iron oxide (SPIO)-labeled cells in vivo. Despite the large number of cell labeling studies that have been performed with SPIO particles of differing size and surface charge, it remains unclear which SPIO configuration provides optimal contrast in nonphagocytic cells. This is largely because contradictory findings have stemmed from the variability and imprecise control over surface charge, the general need and complexity of transfection and/or targeting agents, and the limited number of particle configurations examined in any given study. In the present study, we systematically evaluated the cellular uptake of SPIO in non-phagocytic Tcells over a continuum of particle sizes ranging from 33 nm to nearly 1.5 mu m, with precisely controlled surface properties, and without the need for transfection agents. SPIO labeling of T cells was analyzed by flow cytometry and contrast enhancement was determined by relaxometry. SPIO uptake was dose-dependent and exhibited sigmoidal charge dependence, which was shown to saturate at different levels of functionalization. Efficient labeling of cells was observed for particles up to 300 nm, however, micron-sized particle uptake was limited. Our results show that an unconventional highly cationic particle configuration at 107 nm maximized MR contrast of T cells, outperforming the widely utilized USPIO (< 50 nm). (c) 2008 Elsevier Ltd. All rights reserved.