Visualization of custom-tailored iron oxide nanoparticles chemistry, uptake, and toxicity.
Nanoparticles of iron oxide generated by wearing of vehicles have been modelled with a tailored solution of size-uniform engineered magnetite particles produced by the Bradley reaction, a solvothermal metal-organic approach rendering hydrophilic particles. The latter does not bear any pronounced surface charge in analogy with that originating from anthropogenic sources in the environment. Physicochemical properties of the nanoparticles were thoroughly characterized by a wide range of methods, including XPD, TEM, SEM, DLS and spectroscopic techniques. The magnetite nanoparticles were found to be sensitive for transformation into maghemite under ambient conditions. This process was clearly revealed by Raman spectroscopy for high surface energy magnetite particles containing minor impurities of the hydromaghemite phase and was followed by quantitative measurements with EXAFS spectroscopy. In order to assess the toxicological effects of the produced nanoparticles in humans, with and without surface modification with ATP (a model of bio-corona formed in alveolar liquid), a pathway of potential uptake and clearance was modelled with a sequence of in vitro studies using A549 lung epithelial cells, lymphocyte 221-B cells, and 293T embryonal kidney cells, respectively. Raman microscopy unambiguously showed that magnetite nanoparticles are internalized within the A549 cells after 24 h co-incubation, and that the ATP ligand is retained on the nanoparticles throughout the uptake process. The toxicity of the nanoparticles was estimated using confocal fluorescence microscopy and indicated no principal difference for unmodified and modified particles, but revealed considerably different biochemical responses. The IL-8 cytokine response was found to be significantly lower for the magnetite nanoparticles compared to TiO(2), while an enhancement of ROS was observed, which was further increased for the ATP-modified nanoparticles, implicating involvement of the ATP signalling pathway in the epithelium.
Department of Chemistry, SLU BioCenter, P.O. Box 7015, SE-75007 Uppsala, Sweden. kai.wilkinson@slu.com
Kai
K
Wilkinson
Barbro
B
Ekstrand-Hammarström
Linnea
L
Ahlinder
Karolin
K
Guldevall
Robert
R
Pazik
Leszek
L
Kępiński
Kristina O
KO
Kvashnina
Sergei M
SM
Butorin
Hjalmar
H
Brismar
Björn
B
Önfelt
Lars
L
Österlund
Gulaim A
GA
Seisenbaeva
Vadim G
VG
Kessler
D000255:Adenosine Triphosphate / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D018613:Microscopy, Confocal; D017382:Reactive Oxygen Species / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D014025:Titanium / Q000737:chemistry
D005290:Ferric Compounds; D016209:Interleukin-8; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C009495:titanium dioxide; C000499:ferric oxide; D000255:Adenosine Triphosphate; D014025:Titanium