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@article{1369253,
author = {Štefančíková, Lenka and Lacombe, S and Salado, D and Porcel, E and Pagáčová, Eva and Tillement, O and Lux, François and Depeš, Daniel and Kozubek, Stanislav and Falk, Martin},
article_location = {LONDON},
doi = {http://dx.doi.org/10.1186/s12951-016-0215-8},
keywords = {Radiosensitization; Nanomedicine; Gadolinium; Nanoparticles; DNA double-strand breaks; DNA repair; Radiotherapy; Theranostic},
language = {eng},
issn = {1477-3155},
journal = {JOURNAL OF NANOBIOTECHNOLOGY},
title = {Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells},
url = {http://dx.doi.org/10.1186/s12951-016-0215-8},
volume = {14},
year = {2016}
}
TY - JOUR
ID - 1369253
AU - Štefančíková, Lenka - Lacombe, S - Salado, D - Porcel, E - Pagáčová, Eva - Tillement, O - Lux, François - Depeš, Daniel - Kozubek, Stanislav - Falk, Martin
PY - 2016
TI - Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells
JF - JOURNAL OF NANOBIOTECHNOLOGY
VL - 14
PB - BIOMED CENTRAL LTD
SN - 14773155
KW - Radiosensitization
KW - Nanomedicine
KW - Gadolinium
KW - Nanoparticles
KW - DNA double-strand breaks
KW - DNA repair
KW - Radiotherapy
KW - Theranostic
UR - http://dx.doi.org/10.1186/s12951-016-0215-8
L2 - http://dx.doi.org/10.1186/s12951-016-0215-8
N2 - Background: Tumor targeting of radiotherapy represents a great challenge. The addition of multimodal nanoparticles, such as 3 nm gadolinium-based nanoparticles (GdBNs), has been proposed as a promising strategy to amplify the effects of radiation in tumors and improve diagnostics using the same agents. This singular property named theranostic is a unique advantage of GdBNs. It has been established that the amplification of radiation effects by GdBNs appears due to fast electronic processes. However, the influence of these nanoparticles on cells is not yet understood. In particular, it remains dubious how nanoparticles activated by ionizing radiation interact with cells and their constituents. A crucial question remains open of whether damage to the nucleus is necessary for the radiosensitization exerted by GdBNs (and other nanoparticles). Methods: We studied the effect of GdBNs on the induction and repair of DNA double-strand breaks (DSBs) in the nuclear DNA of U87 tumor cells irradiated with.-rays. For this purpose, we used currently the most sensitive method of DSBs detection based on high-resolution confocal fluorescence microscopy coupled with immunodetection of two independent DSBs markers. Results: We show that, in the conditions where GdBNs amplify radiation effects, they remain localized in the cytoplasm, i.e. do not penetrate into the nucleus. In addition, the presence of GdBNs in the cytoplasm neither increases induction of DSBs by.-rays in the nuclear DNA nor affects their consequent repair. Conclusions: Our results suggest that the radiosensitization mediated by GdBNs is a cytoplasmic event that is independent of the nuclear DNA breakage, a phenomenon commonly accepted as the explanation of biological radiation effects. Considering our earlier recognized colocalization of GdBNs with the lysosomes and endosomes, we revolutionary hypothesize here about these organelles as potential targets for (some) nanoparticles. If confirmed, this finding of cytoplasmically determined radiosensitization opens new perspectives of using nano-radioenhancers to improve radiotherapy without escalating the risk of pathologies related to genetic damage.
ER -
ŠTEFANČÍKOVÁ, Lenka, S LACOMBE, D SALADO, E PORCEL, Eva PAGÁČOVÁ, O TILLEMENT, Fran$\backslash$c cois LUX, Daniel DEPEŠ, Stanislav KOZUBEK and Martin FALK. Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells. \textit{JOURNAL OF NANOBIOTECHNOLOGY}. LONDON: BIOMED CENTRAL LTD, 2016, vol.~14, 15 pp. ISSN~1477-3155. Available from: https://dx.doi.org/10.1186/s12951-016-0215-8.
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