Thioredoxin Reductase Activity Predicts Gold Nanoparticle Radiosensitization Effect

Nanomaterials

卷:9

Stéphane Lucas¹  Anne-Catherine Heuskin¹  Sébastien Penninckx¹  Carine Michiels² 

[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;

关键词: gold nanoparticles;    radiosensitization;    thioredoxin reductase;    radiation;    prognosis;    biochemical mechanism;   

DOI  :  10.3390/nano9020295

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown