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

作　　者：GU JingLi XU HaiFei HAN YeHua DAI Wei HAO Wei WANG Chun Yu GU Ning XU HaiYan CAO JiMin 

机构地区：[1]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 [2]Center of Electromicroscope, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China [3]State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 211189, China [4]Department of Biomedical Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China

出　　处：《Science China(Life Sciences)》2011年第9期793-805,共13页中国科学（生命科学英文版）

基　　金：supported by the National Basic Research Program of China,Ministry of Science and Technology of China (Grant Nos. 2006CB933202 and 2011CB933504) ;the National High Technology Research and Development Program of China (Grant No. 2008AA02Z425);a grant from the National Natural Science Foundation of China (Grant No.81071072)

摘　　要：The potential applications of superparamagnetic iron oxide nanoparticles （SPIONs） in several nanomedical fields have attract- ed 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 mito- sis; 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 hut 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.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.

关 键 词：iron oxide nanoparticles contrast medium MACROPHAGE ENDOCYTOSIS iron metabolism 

分 类 号：Q55[生物学—生物化学] TQ110[化学工程—无机化工]