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超顺磁性氧化铁纳米颗粒在巨噬细胞样 RAW264.7 细胞中的内化途径、代谢命运和生物学效应。

The internalization pathway, metabolic fate and biological effect of superparamagnetic iron oxide nanoparticles in the macrophage-like RAW264.7 cell.

机构信息

Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China.

出版信息

Sci China Life Sci. 2011 Sep;54(9):793-805. doi: 10.1007/s11427-011-4215-5. Epub 2011 Sep 16.

DOI:10.1007/s11427-011-4215-5
PMID:21922429
Abstract

The potential applications of superparamagnetic iron oxide nanoparticles (SPIONs) in several nanomedical fields have attracted intense interest based on the cell-nano interaction. However, the mechanisms underlying cell uptake, the intracellular trail, final fate and the biological effects of SPIONs have not yet been clearly elucidated. Here, we showed that multiple endocytic pathways were involved in the internalization process of SPIONs in the RAW264.7 macrophage. The internalized SPIONs were biocompatible and used three different metabolic pathways: The SPIONs were distributed to daughter cells during mitosis; they were degraded in the lysosome and free iron was released into the intracellular iron metabolic pool; and, the intact SPIONs were potentially exocytosed out of the cells. The internalized SPIONs did not induce cell damage but affected iron metabolism, inducing the upregulation of ferritin light chain at both the mRNA and protein levels and ferroportin 1 at the mRNA level. These results may contribute to the development of nanobiology and to the safe use of SPIONs in medicine when administered as a contrast medium or a drug delivery tool.

摘要

基于细胞-纳米相互作用,超顺磁氧化铁纳米粒子(SPIONs)在多个纳米医学领域的潜在应用引起了人们的浓厚兴趣。然而,SPIONs 的细胞摄取机制、细胞内轨迹、最终命运和生物学效应尚未得到明确阐明。在这里,我们表明,在 RAW264.7 巨噬细胞中,SPIONs 的内化过程涉及多种内吞途径。内化的 SPIONs 具有生物相容性,并使用三种不同的代谢途径:SPIONs 在有丝分裂过程中分配到子细胞中;它们在溶酶体中降解,游离铁释放到细胞内铁代谢池中;完整的 SPIONs 可能被外排到细胞外。内化的 SPIONs 不会引起细胞损伤,但会影响铁代谢,导致铁蛋白轻链在 mRNA 和蛋白质水平以及 ferroportin 1 在 mRNA 水平上调。这些结果可能有助于纳米生物学的发展,并有助于将 SPIONs 作为造影剂或药物输送工具安全地应用于医学。

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