title: Necrotic cell death caused by exposure to graphitic carbon-coated magnetic nanoparticles.
abstract: We synthesized graphitic carbon-coated magnetic nanoparticles (Fe@C NPs) and evaluated their physicochemical properties and mechanism of cytotoxicity in vitro. The structure of these nanocomposites consisted of an iron core encapsulated by a graphitic-carbon shell. The diameter of these Fe@C NPs was 81 ± 14 nm, and the thickness of the carbon layer encapsulating the core was 7.0 ± 0.5 nm. Inhibition of cell proliferation was induced by exposure to Fe@C NPs at doses above 50 μg mL(-1) . The exposed cells did not show increased activation of apoptosis biomarkers such as PARP, caspase-3, caspase-7, and caspase-9, and apoptosis-specific responses such as DNA laddering and annexin V binding to the cell membranes. In addition, the expression levels of autophagy-specific biomarkers such as ATG5 and LC3 after exposure were not enhanced, either. Instead, we observed increased release of lactate dehydrogenase in the culture media and red-fluorescent cell cytosol stained with ethidium homodimer I after the exposure. These results indicated enhanced cell membrane permeability after exposure to Fe@C NPs, probably caused by necrosis. The analysis of the regulatory molecules of cell cycling and proliferation, ERK, p53, and AKT, implied that cell cycle arrest was initiated and the cells were sensitized to necrosis. This necrotic cell death was also observed in carbon shells from Fe@C NPs obtained by removing the metal core. In conclusion, the graphitic carbon-encapsulated magnetic nanoparticles synthesized by one-pot synthesis induced necrotic cell death to human HEK293 cells, which was caused by graphitic carbon surface encapsulating the metal core.
authors.affiliation: Nano & Bio Research Division, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 711-873, Republic of Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Energy Systems Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 711-873, Republic of Korea.
authors.forename: Jakkid
authors.initials: J
authors.lastname: Sanetuntikul
authors.affiliation: Department of Energy Systems Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 711-873, Republic of Korea.
authors.forename: Sangaraju
authors.initials: S
authors.lastname: Shanmugam
authors.affiliation: Nano & Bio Research Division, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 711-873, Republic of Korea.
authors.forename: Eunjoo
authors.initials: E
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000633:toxicity*; D006108:Graphite / Q000633:toxicity*; D057809:HEK293 Cells; D006801:Humans; D058185:Magnetite Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D008422:Materials Testing; D053761:Nanocomposites / Q000737:chemistry / Q000633:toxicity / Q000648:ultrastructure; D009336:Necrosis; D010316:Particle Size
chemical_list: D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D058185:Magnetite Nanoparticles; D006108:Graphite
keywords: cell cycle arrest; graphitic carbon-encapsulation; magnetic nanoparticles; nanotoxicity; necrosis