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PAGÁČOVÁ, E. ŠTEFANČÍKOVÁ, L. SCHMIDT-KALER, F. HILDENBRAND, G. VIČAR, T. DEPEŠ, D. LEE, J. BESTVATER, F. LACOMBE, S. PORCEL, E. ROUX, S. WENZ, F. KOPEČNÁ, O. FALKOVÁ, I. HAUSMANN, M. FALK, M.
Original Title
Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy
Type
journal article in Web of Science
Language
English
Original Abstract
From 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 (γ- and X-rays) on the extent, complexity and reparability of radiation-induced γH2AX + 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.
Keywords
metal nanoparticles; cancer radiotherapy; tumor cell radiosensitization; DNA damage; DNA repair; DNA double strand breaks (DSBs); super-resolution microscopy; single-molecule localization microscopy (SMLM); DNA repair foci; damage to lysosomes
Authors
PAGÁČOVÁ, E.; ŠTEFANČÍKOVÁ, L.; SCHMIDT-KALER, F.; HILDENBRAND, G.; VIČAR, T.; DEPEŠ, D.; LEE, J.; BESTVATER, F.; LACOMBE, S.; PORCEL, E.; ROUX, S.; WENZ, F.; KOPEČNÁ, O.; FALKOVÁ, I.; HAUSMANN, M.; FALK, M.
Released
30. 1. 2019
Publisher
MDPI
Location
ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
ISBN
1422-0067
Periodical
International Journal of Molecular Sciences
Year of study
20
Number
3
State
Swiss Confederation
Pages from
1
Pages to
25
Pages count
URL
https://www.mdpi.com/1422-0067/20/3/588
Full text in the Digital Library
http://hdl.handle.net/11012/195683
BibTex
@article{BUT159777, author="Eva {Pagáčová} and Lenka {Štefančíková} and Franz {Schmidt-Kaler} and Georg {Hildenbrand} and Tomáš {Vičar} and Daniel {Depeš} and Jin-Ho {Lee} and Felix {Bestvater} and Sandrine {Lacombe} and Erika {Porcel} and Stéphane {Roux} and Frederik {Wenz} and Olga {Kopečná} and Iva {Falková} and Michael {Hausmann} and Martin {Falk}", title="Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy", journal="International Journal of Molecular Sciences", year="2019", volume="20", number="3", pages="1--25", doi="10.3390/ijms20030588", issn="1422-0067", url="https://www.mdpi.com/1422-0067/20/3/588" }