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Nanomaterials 2019, 9(2), 295; https://doi.org/10.3390/nano9020295

Thioredoxin Reductase Activity Predicts Gold Nanoparticle Radiosensitization Effect

1
Research Center for the Physics of Matter and Radiation (PMR-LARN), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium
2
Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium
*
Author to whom correspondence should be addressed.
Received: 30 January 2019 / Revised: 13 February 2019 / Accepted: 15 February 2019 / Published: 19 February 2019
(This article belongs to the Special Issue Biomedical Applications of Nanoparticles)
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Abstract

Gold nanoparticles (GNPs) have been shown to be effective contrast agents for imaging and emerge as powerful radiosensitizers, constituting a promising theranostic agent for cancer. Although the radiosensitization effect was initially attributed to a physical mechanism, an increasing number of studies challenge this mechanistic hypothesis and evidence the importance of oxidative stress in this process. This work evidences the central role played by thioredoxin reductase (TrxR) in the GNP-induced radiosensitization. A cell type-dependent reduction in TrxR activity was measured in five different cell lines incubated with GNPs leading to differences in cell response to X-ray irradiation. Correlation analyses demonstrated that GNP uptake and TrxR activity inhibition are associated to a GNP radiosensitization effect. Finally, Kaplan-Meier analyses suggested that high TrxR expression is correlated to low patient survival in four different types of cancer. Altogether, these results enable a better understanding of the GNP radiosensitization mechanism, which remains a mandatory step towards further use in clinic. Moreover, they highlight the potential application of this new treatment in a personalized medicine context. View Full-Text
Keywords: gold nanoparticles; radiosensitization; thioredoxin reductase; radiation; prognosis; biochemical mechanism gold nanoparticles; radiosensitization; thioredoxin reductase; radiation; prognosis; biochemical mechanism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Penninckx, S.; Heuskin, A.-C.; Michiels, C.; Lucas, S. Thioredoxin Reductase Activity Predicts Gold Nanoparticle Radiosensitization Effect. Nanomaterials 2019, 9, 295.

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