title: The internalization pathway, metabolic fate and biological effect of superparamagnetic iron oxide nanoparticles in the macrophage-like RAW264.7 cell.
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.
authors.affiliation: 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.
authors.forename: Jingli
authors.initials: J
authors.lastname: Gu
authors.forename: Haifei
authors.initials: H
authors.lastname: Xu
authors.forename: Yehua
authors.initials: Y
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Wei
authors.initials: W
authors.lastname: Hao
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Jimin
authors.initials: J
authors.lastname: Cao
mesh_terms: D000818:Animals; D001483:Base Sequence; D001672:Biocompatible Materials; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D004705:Endocytosis; D005290:Ferric Compounds / Q000378:metabolism*; D005434:Flow Cytometry; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D013058:Mass Spectrometry; D053768:Metal Nanoparticles; D051379:Mice; D046529:Microscopy, Electron, Transmission; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001672:Biocompatible Materials; D017931:DNA Primers; D005290:Ferric Compounds; C000499:ferric oxide