Coating-dependent induction of cytotoxicity and genotoxicity of iron oxide nanoparticles.
Surface coatings of nanoparticles (NPs) are known to influence advantageous features of NPs as well as potential toxicity. Iron oxide (Fe3O4) NPs are applied for both medical diagnostics and targeted drug delivery. We investigated the potential cytotoxicity and genotoxicity of uncoated iron oxide (U-Fe3O4) NPs in comparison with oleate-coated iron oxide (OC-Fe3O4) NPs. Testing was performed in vitro in human lymphoblastoid TK6 cells and in primary human blood cells. For cytotoxicity testing, relative growth activity, trypan blue exclusion, (3)H-thymidine incorporation and cytokinesis-block proliferation index were assessed. Genotoxicity was evaluated by the alkaline comet assay for detection of strand breaks and oxidized purines. Particle characterization was performed in the culture medium. Cellular uptake, morphology and pathology were evaluated by electron microscopy. U-Fe3O4 NPs were found not to be cytotoxic (considering interference of NPs with proliferation test) or genotoxic under our experimental conditions. In contrast, OC-Fe3O4 NPs were cytotoxic in a dose-dependent manner, and also induced DNA damage, indicating genotoxic potential. Intrinsic properties of sodium oleate were excluded as a cause of the toxic effect. Electron microscopy data were consistent with the cytotoxicity results. Coating clearly changed the behaviour and cellular uptake of the NPs, inducing pathological morphological changes in the cells.
Health Effects Laboratory, Department of Environmental Chemistry, NILU, Norwegian Institute for Air Research , Kjeller , Norway .
Zuzana
Z
Magdolenova
Martina
M
Drlickova
Kristi
K
Henjum
Elise
E
Rundén-Pran
Jana
J
Tulinska
Dagmar
D
Bilanicova
Giulio
G
Pojana
Alena
A
Kazimirova
Magdalena
M
Barancokova
Miroslava
M
Kuricova
Aurelia
A
Liskova
Marta
M
Staruchova
Fedor
F
Ciampor
Ivo
I
Vavra
Yolanda
Y
Lorenzo
Andrew
A
Collins
Alessandra
A
Rinna
Lise
L
Fjellsbø
Katarina
K
Volkovova
Antonio
A
Marcomini
Mahmood
M
Amiry-Moghaddam
Maria
M
Dusinska
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D003603:Cytotoxins / Q000737:chemistry* / Q000633:toxicity*; D004249:DNA Damage; D005290:Ferric Compounds / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D009153:Mutagens / Q000737:chemistry* / Q000633:toxicity*; D013499:Surface Properties
D003603:Cytotoxins; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D009153:Mutagens; C000499:ferric oxide
Coating; DNA damage; cytotoxicity; genotoxicity; human lymphoblastoid TK6 cells; human peripheral lymphocytes; iron oxide; nanoparticles