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

0504530 - BFÚ 2020 RIV CH eng J - Článek v odborném periodiku
Pagáčová, Eva - Štefančíková, Lenka - Schmidt-Kaler, F. - Hildenbrand, G. - Vicar, T. - Depeš, Daniel - Lee, J.H. - Bestvater, F. - Lacombe, S. - Porcel, E. - Roux, S. - Wenz, F. - Kopečná, Olga - Falková, Iva - Hausmann, M. - Falk, Martin
Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy.
International Journal of Molecular Sciences. Roč. 20, č. 3 (2019), č. článku 588. E-ISSN 1422-0067
Grant CEP: GA MZd NV16-29835A; GA ČR(CZ) GA16-12454S
Institucionální podpora: RVO:68081707
Klíčová slova: complex cell responses * gold nanoparticles * dna-damage * radiation-therapy
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.556, rok: 2019
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/20/3/588/pdf

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 (- 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 approachsingle 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.
Trvalý link: http://hdl.handle.net/11104/0296141