New Strategies to Prolong the In Vivo Life Span of Iron-Based Contrast Agents for MRI
New Strategies to Prolong the In Vivo Life Span of Iron-Based Contrast Agents for MRI
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DOI：
10.1371/journal.pone.0078542
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发表时间：
2013-10-25
期刊：
影响因子：
3.7
通讯作者：
Magnani, Mauro
中科院分区：
文献类型：
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作者：
Antonelli, Antonella;Sfara, Carla;Magnani, Mauro
超顺磁性氧化铁（SPIO）和超小超顺磁性氧化铁（USPIO）纳米粒子已被开发为磁共振成像（MRI）造影剂。氧化铁纳米粒子，成为超顺磁性，如果核心颗粒直径是（类似于）30 nm或更小，目前的R1和R2弛豫比那些常规的顺磁性钆螯合物高得多。通常，这些磁性颗粒涂覆有生物相容性聚合物，其防止胶体悬浮液的团聚并改善其血液分布曲线。尽管它们作为MRI血液造影剂的潜力，但氧化铁纳米颗粒的生物医学应用仍然受到限制，因为它们的血管内半衰期仅为几个小时;这种纳米颗粒被网状内皮系统（RES）的巨噬细胞从血流中迅速清除。为了增加这些MRI造影剂在血流中的寿命，我们提出了通过细胞膜孔的瞬时打开将SPIO纳米颗粒包封在红细胞（RBC）中。我们最近报道了通过将我们的加载程序应用于具有不同化学物理特性（如尺寸和涂层剂）的几种SPIO纳米颗粒所获得的结果。在目前的研究中，我们表明，铁基造影剂在小鼠血流中的寿命延长到12天后，静脉注射小鼠SPIO负载的红细胞。此外，我们开发了一种动物模型，其涉及用氯膦酸盐预处理动物以诱导组织巨噬细胞的瞬时抑制，然后注射人SPIO负载的RBC，这使得可以包封比鼠SPIO负载的RBC（1.4-3.55mM Fe）更高的纳米颗粒浓度（5.3-16.7mM Fe）。数据显示，当使用人RBC作为更有能力的SPIO纳米颗粒容器与组织巨噬细胞的消耗相结合时，动物血液中的Fe浓度比通过使用负载有SPIO的鼠RBC获得的铁浓度高2-3倍。
Superparamagnetic iron oxide (SPIO) and ultra small superparamagnetic iron oxide (USPIO) nanoparticles have been developed as magnetic resonance imaging (MRI) contrast agents. Iron oxide nanoparticles, that become superparamagnetic if the core particle diameter is (similar to) 30nm or less, present R1 and R2 relaxivities which are much higher than those of conventional paramagnetic gadolinium chelates. Generally, these magnetic particles are coated with biocompatible polymers that prevent the agglomeration of the colloidal suspension and improve their blood distribution profile. In spite of their potential as MRI blood contrast agents, the biomedical application of iron oxide nanoparticles is still limited because of their intravascular half-life of only few hours; such nanoparticles are rapidly cleared from the bloodstream by macrophages of the reticulo-endothelial system (RES). To increase the life span of these MRI contrast agents in the bloodstream we proposed the encapsulation of SPIO nanoparticles in red blood cells (RBCs) through the transient opening of cell membrane pores. We have recently reported results obtained by applying our loading procedure to several SPIO nanoparticles with different chemical physical characteristics such as size and coating agent. In the current investigation we showed that the life span of iron-based contrast agents in the mice bloodstream was prolonged to 12 days after the intravenous injection of murine SPIO-loaded RBCs. Furthermore, we developed an animal model that implicates the pretreatment of animals with clodronate to induce a transient suppression of tissue macrophages, followed by the injection of human SPIO-loaded RBCs which make it possible to encapsulate nanoparticle concentrations (5.3-16.7mM Fe) higher than murine SPIO-loaded RBCs (1.4-3.55mM Fe). The data showed that, when human RBCs are used as more capable SPIO nanoparticle containers combined with a depletion of tissue macrophages, Fe concentration in animal blood is 2-3 times higher than iron concentration obtained by the use of murine SPIO-loaded RBCs.