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The mechanism of cytotoxic and cytoprotective effects of fullerene (C60) nanoparticles

dc.contributor.advisorTrajković, Vladimir
dc.contributor.otherIsaković, Aleksandra
dc.contributor.otherMarković, Zoran
dc.contributor.otherVolarević, Vladislav
dc.creatorMisirkić Marjanović, Maja
dc.date.accessioned2016-04-03T17:35:33Z
dc.date.available2016-04-03T17:35:33Z
dc.date.available2020-07-03T08:51:35Z
dc.date.issued2015-07-10
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/5056
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=2707
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:10829/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=512260532
dc.description.abstractU ovoj doktorskoj disertaciji ispitivani su citotoksični efekti koloidnih rastvora fulerenskih nanočestica, kao i uticaj mehanohemijski pripremljenih fulerena na citotoksičnost azot monoksida. Zbog sposobnosti da indukuju ćelijsku smrt u određenim uslovima, fulereni C60 predstavljaju potencijalne antitumorske i toksične agense. Koloidni rastvor kristalnog C60 (nC60) je izuzetno toksičan, ali mehanizmi njegove citotoksičnosti još uvek nisu dovoljno ispitani ni razjašnjeni. U ovoj studiji korišćena su tri različita načina pripreme nC60 rastvora: 1. metodom izmene rastvarača u tetrahidrofuranu (THF/nC60), 2. etanolu (EtOH/nC60) ili 3. produženim mešanjem u vodi (H2O/nC60). Kombinovanjem eksperimentalnih analiza i matematičkog modelovanja ispitivani su uslovi pod kojim različiti rastvori nC60 ispoljavaju citotoksičnost posredovanu reaktivnim kiseoničkim vrstama (RKV). Prema sposobnosti da generišu RKV i izazovu mitohondrijalnu depolarizaciju praćenu nekrozom, rastvori nC60 su rangirani sledećim redosledom: THF/nC60 > EtOH/nC60 > H2O/nC60. Matematičko modelovanje produkcije singletnog kiseonika (1O2) pokazuje da sposobnost rastvarača ugrađenog u strukturu fulerenskog kristala da neutrališe 1O2 (THF/nC60 < EtOH/nC60 < H2O/nC60) predstavlja presudni faktor koji određuje sposobnost nanočestice da proizvodi RKV i izaziva ćelijsko oštećenje. Ovi rezultati skreću pažnju na toksikološki aspekt koloidnih fulerena u njihovoj potencijalnoj upotrebi u biomedicini. Fulereni imaju dvojnu prirodu tako da osim što proizvode RKV kada su pobuđeni vidljivom svetlošću, oni deluju i kao ,,skupljači“ slobodnih radikala i ispoljavaju značajna antioksidativna svojstva. Iz tog razloga je, u drugom delu studije, ispitivan uticaj fulerenskih nanočestica na citotoksičnost azot monoksida (NO), veoma reaktivnog slobodnog radikala. Fulerenske nanočestice su pripremljene mehanohemijski potpomognutom kompleksacijom uz korišćenje anjonskog surfaktanta natrijum dodecil sulfata (SDS), makrocikličnog oligosaharidγa -ciklodekstrina (γCDX) ili kopolimera acetat-etilen vinil versatata (EVA-EVV) i karakterisane metodama UV-vis spektroskopije i mikroskopijom atomskih sila (AFM)...sr
dc.description.abstractIn this doctoral dissertation we investigated cytotoxic effects of fullerene colloidal suspensions, as well as the influence of mechanochemically synthesized fullerene C60 nanoparticles on the cytotoxicity of nitric oxide (NO). Because of their ability to induce cell death in certain conditions, fullerenes are potential toxic and anticancer agents. Colloidal suspension of crystalline C60 (nC60) is very toxic, but the mechanisms of its cytotoxicity are not completely explained. By combining experimental analysis and mathematical modeling, the requirements for the reactive oxygen species (ROS)- mediated cytotoxicity of different nC60 suspensions were investigated. Colloidal suspensions of nC60 were prepared by solvent exchange method in tetrahydrofuran (THF/nC60) and ethanol (EtOH/nC60), or by extended mixing in water (H2O/nC60). With regard to their capacity to generate RKV and cause mitochondrial depolarization followed by necrotic cell death, the nC60 suspensions were ranked in the following order: THF/nC60 > EtOH/nC60 > aqu/nC60. Mathematical modeling of singlet oxygen (1O2) generation indicates that the 1O2-quenching power (THF/ nC60 < EtOH/nC6 0<H2O/nC60) of the solvent intercalated in the fullerene crystals determines their ability to produce ROS and cause cell damage. These results could have important implications for the toxicology and biomedical application of colloidal fullerenes. Fullerenes are molecules with dual properties, able to produce ROS when photoexcited, but also to scavenge free radicals and exert antioxidant action. In order to assess the latter, the influence of fullerene C60 nanoparticles on the cytotoxicity of a highly reactive free radical nitric oxide (NO) was investigated. Fullerene nanoparticles were prepared by mechanochemically assisted complexation with anionic surfactant sodium dodecyl sulfate, macrocyclic oligosaccharide γ-cyclodextrin or the copolymer ethylene vinyl acetate–ethylene vinyl versatate, and characterized by UV–vis and atomic force microscopy (AFM)...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173053/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectNanočesticesr
dc.subjectNanoparticlesen
dc.subjectCytotoxicityen
dc.subjectFree radicalsen
dc.subjectNitric oxideen
dc.subjectApoptosisen
dc.subjectCitotoksičnostsr
dc.subjectSlobodni radikalisr
dc.subjectAzot monoksidsr
dc.subjectApoptozasr
dc.titleMehanizmi citotoksičnog i citoprotektivnog dejstva fulerenskih (C60) nanočesticasr
dc.titleThe mechanism of cytotoxic and cytoprotective effects of fullerene (C60) nanoparticlesen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dcterms.abstractТрајковић, Владимир; Исаковић, Aлександра; Марковић, Зоран; Воларевић, Владислав; Мисиркић Марјановић, Маја; Механизми цитотоксичног и цитопротективног дејства фулеренских (Ц60) наночестица; Механизми цитотоксичног и цитопротективног дејства фулеренских (Ц60) наночестица;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/10274/Disertacija706.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/10275/Maja_Misirkic_Marjanovic_Izvestaj_Komisije_MDF.pdf


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