The effect of carboxydextran-coated superparamagnetic iron oxide nanoparticles on c-Jun N-terminal kinase-mediated apoptosis in human macrophages
The effect of carboxydextran-coated superparamagnetic iron oxide nanoparticles on c-Jun N-terminal kinase-mediated apoptosis in human macrophages
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DOI：
10.1016/j.biomaterials.2010.03.023
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发表时间：
2010-07-01
期刊：
影响因子：
14
通讯作者：
Simmet，Thomas
中科院分区：
文献类型：
--
作者：
Lunov，Oleg;Syrovets，Tatiana;Simmet，Thomas
超顺磁性氧化铁纳米颗粒经常用于细胞标记或作为诊断造影剂，但分析其对免疫细胞影响的研究仍然很少。在这里，我们研究了纳米羧基葡聚糖包被的超顺磁性氧化铁（SPIO）和超小超顺磁性氧化铁（USPIO）如何影响人类巨噬细胞。 1 小时内，SPIO 和 USPIO 均被巨噬细胞迅速吸收。共聚焦显微镜显示，24 小时后，颗粒几乎完全位于溶酶体室内。持续培养巨噬细胞数天与 c-Jun N 末端激酶 (JNK) 途径的长期激活引起的细胞凋亡诱导有关。 JNK 激活是由于活性氧水平显着升高，而用纳米粒子处理的巨噬细胞不产生 TNF-α。与 SPIO 相比，USPIO 诱导更明显的生化改变和细胞毒性，这可以被 JNK 抑制剂 V 拮抗。或者，用 Trolox™ 或 N-乙酰基-L-半胱氨酸（两种功能不同的活性氧清除剂）处理巨噬细胞，消除了 JNK 激活和随后的细胞毒性作用。这些数据表明，基于纳米超顺磁性氧化铁的造影剂在人巨噬细胞中发挥细胞毒性，可以与自由基清除剂功能性拮抗。
Superparamagnetic iron oxide nanoparticles are frequently used for cell labeling or as diagnostic contrast media, yet studies analyzing their effects on immune cells remain scarce. Here we investigated how nanosized carboxydextran-coated superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) might affect human macrophages. Within 1 h, both SPIO and USPIO were rapidly taken up by macrophages. Confocal microscopy revealed that after 24 h the particles were almost exclusively localized within the lysosomal compartment. Continued cultivation of the macrophages for several days was associated with apoptosis induction caused by a long-lasting activation of the c-Jun N-terminal kinase (JNK) pathway. JNK activation was due to significantly elevated levels of reactive oxygen species, whereas no TNF-α was produced by the macrophages treated with nanoparticles. Compared to SPIO, USPIO induced more pronounced biochemical alterations and cytotoxicity, which could be antagonized by the JNK inhibitor V. Alternatively, treatment of macrophages with Trolox™ or N-acetyl-l-cysteine, two functionally different scavengers of reactive oxygen species, abolished both the JNK activation and the subsequent cytotoxic effects. These data indicate that nanosized superparamagnetic iron oxide-based contrast media exert cytotoxicity in human macrophages that can be functionally antagonized with radical scavengers.