Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

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dc.contributor.authorPagáčová, Evacs
dc.contributor.authorŠtefančíková, Lenkacs
dc.contributor.authorSchmidt-Kaler, Franzcs
dc.contributor.authorHildenbrand, Georgcs
dc.contributor.authorVičar, Tomášcs
dc.contributor.authorDepeš, Danielcs
dc.contributor.authorLee, Jin-Hocs
dc.contributor.authorBestvater, Felixcs
dc.contributor.authorLacombe, Sandrinecs
dc.contributor.authorPorcel, Erikacs
dc.contributor.authorRoux, Stéphanecs
dc.contributor.authorWenz, Frederikcs
dc.contributor.authorKopečná, Olgacs
dc.contributor.authorFalková, Ivacs
dc.contributor.authorHausmann, Michaelcs
dc.contributor.authorFalk, Martincs
dc.coverage.issue3cs
dc.coverage.volume20cs
dc.date.accessioned2020-11-25T15:54:33Z
dc.date.available2020-11-25T15:54:33Z
dc.date.issued2019-01-30cs
dc.description.abstractFrom the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the “physics” behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)), cancer cell types (HeLa, U87, and SKBr3), and doses (up to 4 Gy) of low-Linear Energy Transfer (LET) ionizing radiation (- and X-rays) on the extent, complexity and reparability of radiation-induced H2AX + 53BP1 foci, the markers of double stand breaks (DSBs). Firstly, we sensitively compared the focus presence in nuclei during a long period of time post-irradiation (24 h) in spatially (three-dimensionally, 3D) fixed cells incubated and non-incubated with Pt nanoparticles by means of high-resolution immunofluorescence confocal microscopy. The data were compared with our preliminary results obtained for Au nanoparticles and recently published results for gadolinium (Gd) nanoparticles of approximately the same size (2–3 nm). Next, we introduced a novel super-resolution approach—single molecule localization microscopy (SMLM)—to study the internal structure of the repair foci. In these experiments, 10 nm Au nanoparticles were used that could be also visualized by SMLM. Altogether, the data show that different nanoparticles may or may not enhance radiation damage to DNA, so multi-parameter effects have to be considered to better interpret the radiosensitization. Based on these findings, we discussed on conclusions and contradictions related to the effectiveness and presumptive mechanisms of the cell radiosensitization by nanoparticles. We also demonstrate that SMLM offers new perspectives to study internal structures of repair foci with the goal to better evaluate potential differences in DNA damage patterns.en
dc.formattextcs
dc.format.extent1-25cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationInternational Journal of Molecular Sciences. 2019, vol. 20, issue 3, p. 1-25.en
dc.identifier.doi10.3390/ijms20030588cs
dc.identifier.issn1422-0067cs
dc.identifier.other159777cs
dc.identifier.urihttp://hdl.handle.net/11012/195683
dc.language.isoencs
dc.publisherMDPIcs
dc.relation.ispartofInternational Journal of Molecular Sciencescs
dc.relation.urihttps://www.mdpi.com/1422-0067/20/3/588cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1422-0067/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectmetal nanoparticlesen
dc.subjectcancer radiotherapyen
dc.subjecttumor cell radiosensitizationen
dc.subjectDNA damageen
dc.subjectDNA repairen
dc.subjectDNA double strand breaks (DSBs)en
dc.subjectsuper-resolution microscopyen
dc.subjectsingle-molecule localization microscopy (SMLM)en
dc.subjectDNA repair focien
dc.subjectdamage to lysosomesen
dc.titleChallenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapyen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-159777en
sync.item.dbtypeVAVen
sync.item.insts2020.11.25 16:54:33en
sync.item.modts2020.11.25 16:14:11en
thesis.grantorVysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií. Ústav biomedicínského inženýrstvícs
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