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超顺磁性铁纳米粒子(SPION)已在纳米医学等诸多领域开始应用,其相关研究也受到了广泛关注,但有关磁性纳米粒子进入细胞的方式、代谢归宿及细胞学效应仍不完全清楚.本研究发现,几乎所有的内吞信号通路都参与了SPION进入RAW264.7巨噬细胞的过程.SPION入胞后主要有3种代谢途径:(1)随有丝分裂进入子代细胞;(2)经溶酶体降解释放游离铁离子进入细胞的铁代谢库;(3)可能通过胞吐作用被排至细胞外.SPION入胞后有很好的生物相容性,对细胞活力、活性氧(ROS)生成及线粒体膜电位等无显著影响,但SPION入胞后对胞内的铁代谢有一定影响,能使贮铁蛋白L(ferritin-L)的mRNA和蛋白表达均升高,运铁蛋白1(ferroportin1)在mRNA水平表达升高,但蛋白质水平未见明显变化,且上述两种蛋白质表达的变化不是通过影响铁调节蛋白2(IRP2)实现的.上述发现为深入揭示纳米粒子的入胞机制及磁性纳米粒子在医学上的安全应用提供了实验依据.
Superparamagnetic iron nanoparticles (SPION) have been used in many fields such as nanomedicine, and their related researches have drawn more and more attention. However, the way of magnetic nanoparticles entering cells, metabolic homeostasis and cytological effects are still not fully understood. It has been found that almost all endocytic signaling pathways are involved in the process of SPION entry into RAW264.7 macrophages. There are three main metabolic pathways after SPION entry into the cell: (1) entry into progeny cells with mitosis; (2) (3) may be exocytosed by exocytosis.SPION into the cell after a good biocompatibility, on cell viability, reactive oxygen species (ROS) Generation and mitochondrial membrane potential had no significant effect. However, the intracellular iron metabolism was affected by SPION, and the mRNA and protein expression of ferritin-L were increased. The expression of transferrin 1 ( ferroportin1) was elevated at the mRNA level but no significant changes were observed in the protein levels, and the changes of these two proteins were not mediated by IRP2. Magnetic nano Particles in the medical safety applications provide experimental basis.