Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells

ŠTEFANČÍKOVÁ, Lenka, S LACOMBE, D SALADO, E PORCEL, Eva PAGÁČOVÁ, O TILLEMENT, François LUX, Daniel DEPEŠ, Stanislav KOZUBEK and Martin FALK. Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells. 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.

Basic information

Original name

Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells

Authors

ŠTEFANČÍKOVÁ, Lenka, S LACOMBE, D SALADO, E PORCEL, Eva PAGÁČOVÁ, O TILLEMENT, François LUX, Daniel DEPEŠ, Stanislav KOZUBEK and Martin FALK

Edition

JOURNAL OF NANOBIOTECHNOLOGY, LONDON, BIOMED CENTRAL LTD, 2016, 1477-3155

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Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.946

DOI

http://dx.doi.org/10.1186/s12951-016-0215-8

UT WoS

000381674400002

Keywords in English

Radiosensitization; Nanomedicine; Gadolinium; Nanoparticles; DNA double-strand breaks; DNA repair; Radiotherapy; Theranostic

Tags

International impact, Reviewed

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Abstract

V originále

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.