Superparamagnetic iron oxide nanoparticles (SPION) have attracted great attention not only for therapeutic applications but also as an alternative magnetic resonance imaging (MRI) contrast agent that helps visualize liver tumors during MRI-guided stereotactic body radiotherapy (SBRT). SPION can provide functional imaging of liver parenchyma based upon its uptake by the hepatic resident macrophages or Kupffer cells with a relative enhancement of malignant tumors that lack Kupffer cells. However, the radiomodulating properties of SPION on liver macrophages are not known. Utilizing human monocytic THP-1 undifferentiated and differentiated cells, we characterized the effect of ferumoxytol (Feraheme®), a carbohydrate-coated ultrasmall SPION agent at clinically relevant concentration and therapeutically relevant doses of gamma radiation on cultured cells in vitro. We showed that ferumoxytol affected both monocytes and macrophages, increased the resistance of monocytes to radiation-induced cell death and inhibition of cell activity, and supported the anti-inflammatory phenotype of human macrophages under radiation. Its effect on human cells depended on the duration of SPION uptake and was radiation dose-dependent. The results of this pilot study support a strong mechanism-based optimization of SPION-enhanced MRI-guided liver SBRT for primary and metastatic liver tumors, especially in patients with liver cirrhosis awaiting a liver transplant.
超顺磁性氧化铁纳米颗粒（SPION）不仅在治疗应用领域备受关注，同时也作为一种替代性磁共振成像（MRI）对比剂，在MRI引导的立体定向体部放疗（SBRT）中助力肝脏肿瘤的可视化。SPION通过被肝脏驻留巨噬细胞（即库普弗细胞）摄取，能够实现肝实质的功能成像，并相对增强缺乏库普弗细胞的恶性肿瘤的显影效果。然而，SPION对肝脏巨噬细胞的放射调节特性尚不明确。本研究利用人单核细胞THP-1未分化及分化细胞，在体外培养体系中，以临床相关浓度评估了碳水化合物包被的超小型SPION制剂——菲立磁（Feraheme®），结合治疗相关剂量的γ射线辐射对培养细胞的影响。结果表明，菲立磁对单核细胞和巨噬细胞均产生影响：它增强了单核细胞对辐射诱导的细胞死亡及细胞活性抑制的抵抗能力，并在辐射条件下支持人巨噬细胞向抗炎表型转化。其对人类细胞的作用效果取决于SPION摄取的持续时间，且具有辐射剂量依赖性。这项初步研究的结果为基于机制优化SPION增强MRI引导的肝脏SBRT治疗原发性及转移性肝肿瘤提供了有力支持，尤其适用于等待肝移植的肝硬化患者。
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