Mehanizmi citotoksičnog i citoprotektivnog dejstva fulerenskih (C60) nanočestica
The mechanism of cytotoxic and cytoprotective effects of fullerene (C60) nanoparticles
Doctoral thesis (Published version)
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In this doctoral dissertation we investigated cytotoxic effects of fullerene colloidalsuspensions, as well as the influence of mechanochemically synthesized fullerene C60nanoparticles on the cytotoxicity of nitric oxide (NO). Because of their ability to inducecell death in certain conditions, fullerenes are potential toxic and anticancer agents.Colloidal suspension of crystalline C60 (nC60) is very toxic, but the mechanisms of itscytotoxicity are not completely explained. By combining experimental analysis andmathematical modeling, the requirements for the reactive oxygen species (ROS)-mediated cytotoxicity of different nC60 suspensions were investigated. Colloidalsuspensions of nC60 were prepared by solvent exchange method in tetrahydrofuran(THF/nC60) and ethanol (EtOH/nC60), or by extended mixing in water (H2O/nC60). Withregard to their capacity to generate RKV and cause mitochondrial depolarizationfollowed by necrotic cell death, the nC60 suspensions were ranked in the followingorder: THF/nC60 > EtOH/nC60 > aqu/nC60. Mathematical modeling of singlet oxygen(1O2) generation indicates that the 1O2-quenching power (THF/ nC60 < EtOH/nC60<H2O/nC60) of the solvent intercalated in the fullerene crystals determines their abilityto produce ROS and cause cell damage. These results could have important implicationsfor the toxicology and biomedical application of colloidal fullerenes.Fullerenes are molecules with dual properties, able to produce ROS whenphotoexcited, but also to scavenge free radicals and exert antioxidant action. In order toassess the latter, the influence of fullerene C60 nanoparticles on the cytotoxicity of ahighly reactive free radical nitric oxide (NO) was investigated. Fullerene nanoparticleswere prepared by mechanochemically assisted complexation with anionic surfactantsodium dodecyl sulfate, macrocyclic oligosaccharide γ-cyclodextrin or the copolymerethylene vinyl acetate–ethylene vinyl versatate, and characterized by UV–vis andatomic force microscopy (AFM)...
Keywords:Nanoparticles; Cytotoxicity; Free radicals; Nitric oxide; Apoptosis
Source:University of Belgrade, School of Medicine, 2015, 1-79