title: Comparative cytotoxicity studies of carbon-encapsulated iron nanoparticles in murine glioma cells.
abstract: Carbon-encapsulated iron nanoparticles (CEINs) have recently emerged as a new class of magnetic nanomaterials with a great potential for an increasing number of biomedical applications. To address the current deficient knowledge of cellular responses due to CEIN exposures, we focused on the investigation of internalization profile and resulting cytotoxic effects of CEINs (0.0001-100 μg/ml) in murine glioma cells (GL261) in vitro. The studied CEIN samples were characterized (TEM, FT-IR, Zeta potential, Boehm titration) and examined as raw and purified nanomaterials with various surface chemistry composition. Of the four type CEINs (the mean diameter 47-56 nm) studied here, the as-synthesized raw nanoparticles (Fe@C/Fe) exhibited high cytotoxic effects on the plasma cell membrane (LDH, Calcein AM/PI) and mitochondria (MTT, JC-1) causing some pro-apoptotic evens (Annexin V/PI) in glioma cells. The effects of the purified (Fe@C) and surface-modified (Fe@C-COOH and Fe@C-(CH2)2COOH) CEINs were found in quite similar patterns; however, most of these cytotoxic events were slightly diminished compared to those induced by Fe@C/Fe. The study showed that the surface-functionalized CEINs affected the cell cycle progression in both S and G2/M phases to a greater extent compared to that of the rest of nanoparticles studied to data. Taken all together, the present results highlight the importance of the rational design of CEINs as their physicochemical features such as morphology, hydrodynamic size, impurity profiles, and especially surface characteristics are critical determinants of different cytotoxic responses.
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University of Warsaw, ul. S. Banacha 1, 02-097 Warsaw, Poland. Electronic address: ireneusz.grudzinski@wum.edu.pl.
authors.forename: Ireneusz P
authors.initials: IP
authors.lastname: Grudzinski
authors.affiliation: Department of Physical Chemistry, Faculty of Chemistry, Warsaw University, ul. L. Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Bystrzejewski
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University of Warsaw, ul. S. Banacha 1, 02-097 Warsaw, Poland.
authors.forename: Monika A
authors.initials: MA
authors.lastname: Cywinska
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University of Warsaw, ul. S. Banacha 1, 02-097 Warsaw, Poland.
authors.forename: Anita
authors.initials: A
authors.lastname: Kosmider
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Warsaw University of Technology, ul. S. Noakowskiego 3, 00-664 Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Poplawska
authors.affiliation: Department of Clinical Radiology, Faculty of Medicine, Medical University of Warsaw, ul. S. Banacha 1a, 02-097 Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Cieszanowski
authors.affiliation: Department of Pharmaceutical Chemistry, National Medicinal Institute, ul. Chelmska 30/34, 00-725 Warsaw, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Fijalek
authors.affiliation: Analytic Centre, University of Life Sciences, ul. J. Ciszewskiego 8, 02-786 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Ostrowska
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002244:Carbon / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005910:Glioma / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D057446:Hydrodynamics; D007501:Iron / Q000737:chemistry*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D009336:Necrosis; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity
chemical_list: D002244:Carbon; D007501:Iron; D007770:L-Lactate Dehydrogenase
keywords: Carbon encapsulates; Cytotoxicity; Iron nanoparticles; Murine glioma cells (GL261); Surface functionalization