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Mehanizmi citotoksičnog i citoprotektivnog dejstva fulerenskih (C60) nanočestica
The mechanism of cytotoxic and cytoprotective effects of fullerene (C60) nanoparticles
dc.contributor.advisor | Trajković, Vladimir | |
dc.contributor.other | Isaković, Aleksandra | |
dc.contributor.other | Marković, Zoran | |
dc.contributor.other | Volarević, Vladislav | |
dc.creator | Misirkić Marjanović, Maja | |
dc.date.accessioned | 2017-11-23T08:23:59Z | |
dc.date.available | 2017-11-23T08:23:59Z | |
dc.date.issued | 2015 | |
dc.identifier.uri | http://eteze.bg.ac.rs/application/showtheses?thesesId=2707 | |
dc.identifier.uri | https://fedorabg.bg.ac.rs/fedora/get/o:10829/bdef:Content/download | |
dc.identifier.uri | http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=512260532 | |
dc.identifier.uri | http://nardus.mpn.gov.rs/123456789/5056 | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/2437 | |
dc.description.abstract | U ovoj doktorskoj disertaciji ispitivani su citotoksični efekti koloidnih rastvorafulerenskih nanočestica, kao i uticaj mehanohemijski pripremljenih fulerena nacitotoksičnost azot monoksida. Zbog sposobnosti da indukuju ćelijsku smrt u određenimuslovima, fulereni C60 predstavljaju potencijalne antitumorske i toksične agense.Koloidni rastvor kristalnog C60 (nC60) je izuzetno toksičan, ali mehanizmi njegovecitotoksičnosti još uvek nisu dovoljno ispitani ni razjašnjeni. U ovoj studiji korišćena sutri različita načina pripreme nC60 rastvora: 1. metodom izmene rastvarača utetrahidrofuranu (THF/nC60), 2. etanolu (EtOH/nC60) ili 3. produženim mešanjem u vodi(H2O/nC60). Kombinovanjem eksperimentalnih analiza i matematičkog modelovanjaispitivani su uslovi pod kojim različiti rastvori nC60 ispoljavaju citotoksičnostposredovanu reaktivnim kiseoničkim vrstama (RKV). Prema sposobnosti da generišuRKV i izazovu mitohondrijalnu depolarizaciju praćenu nekrozom, rastvori nC60 surangirani sledećim redosledom: THF/nC60 > EtOH/nC60 > H2O/nC60. Matematičkomodelovanje produkcije singletnog kiseonika (1O2) pokazuje da sposobnost rastvaračaugrađenog u strukturu fulerenskog kristala da neutrališe 1O2 (THF/nC60 < EtOH/nC60 <H2O/nC60) predstavlja presudni faktor koji određuje sposobnost nanočestice daproizvodi RKV i izaziva ćelijsko oštećenje. Ovi rezultati skreću pažnju na toksikološkiaspekt koloidnih fulerena u njihovoj potencijalnoj upotrebi u biomedicini.Fulereni imaju dvojnu prirodu tako da osim što proizvode RKV kada supobuđeni vidljivom svetlošću, oni deluju i kao ,,skupljači“ slobodnih radikala iispoljavaju značajna antioksidativna svojstva. Iz tog razloga je, u drugom delu studije,ispitivan uticaj fulerenskih nanočestica na citotoksičnost azot monoksida (NO), veomareaktivnog slobodnog radikala. Fulerenske nanočestice su pripremljene mehanohemijskipotpomognutom kompleksacijom uz korišćenje anjonskog surfaktanta natrijum dodecilsulfata (SDS), makrocikličnog oligosaharidγa -ciklodekstrina (γCDX) ili kopolimeraacetat-etilen vinil versatata (EVA-EVV) i karakterisane metodama UV-visspektroskopije i mikroskopijom atomskih sila (AFM)... | sr |
dc.description.abstract | 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)... | en |
dc.format | application/pdf | |
dc.language | sr | |
dc.publisher | Belgrade: University of Belgrade, School of Medicine | sr |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | University of Belgrade, School of Medicine | sr |
dc.subject | Nanočestice | sr |
dc.subject | Citotoksičnost | sr |
dc.subject | Slobodni radikali | sr |
dc.subject | Azot monoksid | sr |
dc.subject | Apoptoza | sr |
dc.subject | Nanoparticles | en |
dc.subject | Cytotoxicity | en |
dc.subject | Free radicals | en |
dc.subject | Nitric oxide | en |
dc.subject | Apoptosis | en |
dc.title | Mehanizmi citotoksičnog i citoprotektivnog dejstva fulerenskih (C60) nanočestica | sr |
dc.title | The mechanism of cytotoxic and cytoprotective effects of fullerene (C60) nanoparticles | en |
dc.type | doctoralThesis | |
dc.rights.license | BY-NC-ND | |
dcterms.abstract | Трајковић, 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.citation.apa | Misirkić Marjanović, M. (2015). Mehanizmi citotoksičnog i citoprotektivnog dejstva fulerenskih (C60) nanočestica. University of Belgrade, School of Medicine. | |
dc.citation.vancouver | Misirkić Marjanović M. Mehanizmi citotoksičnog i citoprotektivnog dejstva fulerenskih (C60) nanočestica [dissertation]. Belgarde: University of Belgrade, School of Medicine; 2015. 79 p. | |
dc.citation.spage | 1 | |
dc.citation.epage | 79 | |
dc.type.version | publishedVersion | en |
dc.identifier.fulltext | https://radar.ibiss.bg.ac.rs//bitstream/id/232/Misirkic_Marjanovic_Maja_dissertation.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_5056 |