title: Mechanism of cellular uptake and impact of ferucarbotran on macrophage physiology.
abstract: Superparamagnetic iron oxide (SPIO) nanoparticles are contrast agents used for magnetic resonance imaging. Ferucarbotran is a clinically approved SPIO-coated carboxydextran with a diameter of about 45-60 nm. We investigated the mechanism of cellular uptake of Ferucarbotran with a cell model using the murine macrophage cell line Raw 264.7. We observed a dose-dependent uptake of these SPIO particles by spectrophotometer analysis and also a dose-dependent increase in the granularity of the macrophages as determined by flow cytometry. There was a linear correlation between the side scattering mean value and iron content (P<0.001, R(2) = 0. 8048). For evaluation of the endocytotic pathway of these ingested SPIO particles, different inhibitors of the endocytotic pathways were employed. There was a significant decrease of side scattering counts in the cells and a less significant change in signal intensity based on magnetic resonance in the phenylarsine oxide-treated macrophages. After labeling with SPIO particles, the macrophages showed an increase in the production of reactive oxygen species at 2, 24, and 48 h; a decrease in mitochondrial membrane potential at 24 h; and an increase in cell proliferation at 24 h. We concluded that Ferucarbotran was internalized into macrophages via the clathrin-mediated pathway and can change the cellular behavior of these cells after labeling.
authors: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors: Chung-Yi
authors: CY
authors: Yang
authors: Ming-Fong
authors: MF
authors: Tai
authors: Chih-Peng
authors: CP
authors: Lin
authors: Chen-Wen
authors: CW
authors: Lu
authors: Jaw-Lin
authors: JL
authors: Wang
authors: Jong-Kai
authors: JK
authors: Hsiao
authors: Hon-Man
authors: HM
authors: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003287:Contrast Media / Q000494:pharmacology; D003911:Dextrans / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D005434:Flow Cytometry / Q000379:methods; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D009000:Monocytes / Q000166:cytology; D053758:Nanoparticles / Q000737:chemistry; D017382:Reactive Oxygen Species; D012542:Scattering, Radiation; D013053:Spectrophotometry / Q000379:methods; D013997:Time Factors
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C065507:ferumoxides