Assessing carbon-encapsulated iron nanoparticles cytotoxicity in Lewis lung carcinoma cells.
Carbon-encapsulated iron nanoparticles (CEINs) have been considered as attractive candidates for several biomedical applications. In the present study, we synthesized CEINs (the mean diameter 40-80 nm) using a carbon arc route, and the as-synthesized CEINs were characterized (scanning and transmission electron microscopy, dynamic light scattering, turbidimetry, Zeta potential) and further tested as raw and purified nanomaterials containing the carbon surface modified with acidic groups. For cytotoxicity evaluation, we applied a battery of different methods (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase, calcein AM/propidium iodide, annexin V/propidium iodide, JC-1, cell cycle assay, Zeta potential, TEM and inductively coupled plasma mass spectrometry) to address the strategic cytotoxic endpoints of Lewis lung carcinoma cells due to CEIN (0.0001-100 µg ml(-1) ) exposures in vitro. Our studies evidence that incubation of Lewis lung carcinoma cells with CEINs is accompanied in substantial changes of zeta potential in cells and these effects may result in different internalization profiles. The results show that CEINs increased the mitochondrial and cell membrane cytotoxicity; however, the raw CEIN material (Fe@C/Fe) produced higher toxicities than the rest of the CEINs studied to data. The study showed that non-modified CEINs (Fe@C/Fe and Fe@C) elevated some pro-apoptotic events to a greater extent compared to that of the surface-modified CEINs (Fe@C-COOH and Fe@C-(CH2 )2 COOH). They also diminished the mitochondrial membrane potentials. In contrast to non-modified CEINs, the surface-functionalized nanoparticles caused the concentration- and time-dependent arrest of the S phase in cells. Taken all together, our results shed new light on the rational design of CEINs, as their geometry, hydrodynamic and, in particular, surface characteristics are important features in selecting CEINs as future nanomaterials for nanomedicine applications.
Department of Toxicology, Faculty of Pharmacy, Medical University of Warsaw, ul. S. Banacha 1, 02-097, Warsaw, Poland.
Ireneusz P
IP
Grudzinski
Michal
M
Bystrzejewski
Monika A
MA
Cywinska
Anita
A
Kosmider
Magdalena
M
Poplawska
Andrzej
A
Cieszanowski
Zbigniew
Z
Fijalek
Agnieszka
A
Ostrowska
Andrzej
A
Parzonko
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002244:Carbon / Q000737:chemistry / Q000633:toxicity*; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007501:Iron / Q000737:chemistry / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D013054:Spectrophotometry, Atomic; D013499:Surface Properties
D002244:Carbon; D007501:Iron
Apoptosis; Cell cycle; Cytotoxicity; Internalization; Iron-carbon (core-shell) type nanoparticles; Lewis lung carcinoma cells (LLC); Mitochondrial Membrane Potential