交变磁场对负载纳米颗粒的树突状细胞的作用
Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells
摘要：
在这项工作中，主要的，单核细胞衍生的树突状细胞（DC）摄取氧化铁磁性纳米粒子（MNP）的能力进行了评估，并在这些MNP负载的DC使用外部交变磁场（AMFs）诱导选择性细胞死亡的策略。与对照样品相比，在培养5天后，未观察到负载MNP的DC的细胞活力的显著降低。通过磁力测定法测量掺入细胞质中的MNP的量，其证实每个细胞上载1至5 pg的颗粒。这些MNP的细胞内分布，通过透射电子显微镜评估，被发现主要是内体结构。然后使这些细胞经受AMF 30分钟，并检测空白DC（即，不含MNP）基本上保持不受影响。然而，在相同的30分钟暴露于AMF后，观察到先前负载有MNP的DC的存活率从约90%显著降低至2-5%。使用具有正（NH 2+）或负（COOH-）表面官能团的MNP获得相同的结果。尽管AMF对负载MNP的DC的应用诱导了大量细胞死亡，但掺入的磁性颗粒的量并没有提高细胞培养物的温度。使用扫描电子显微镜观察到磁场应用后细胞结构的明显形态学变化。因此，由MNP产生的局部损伤可能是AMF下MNP负载的DC选择性细胞死亡的主要机制。基于这些细胞逃避网状内皮系统的能力，这些复合物与AMF的结合应被认为是肿瘤治疗的潜在有力工具。
英文摘要：
In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The amount of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1 to 5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min, and the viability of the blank DCs (i.e., without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH2+) or negative (COOH-) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the amount of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.
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