The role of thioredoxin reductase in gold nanoparticle radiosensitization effects

被引:44
作者
Penninckx, Sebastien [1 ]
Heuskin, Anne-Catherine [1 ]
Michiels, Carine [2 ]
Lucas, Stephane [1 ]
机构
[1] Univ Namur, Namur Res Inst Life Sci NARILIS, Res Ctr Phys Matter & Radiat PMR LARN, Rue Bruxelles 61, B-5000 Namur, Belgium
[2] Univ Namur, URBC, Namur Res Inst Life Sci NARILIS, Rue Bruxelles 61, B-5000 Namur, Belgium
关键词
biological mechanism; gold nanoparticles; proton irradiation; radiosensitization; thioredoxin reductase; GADOLINIUM-BASED NANOPARTICLES; RADIATION ENHANCEMENT; TUMOR-CELLS; X-RAY; RADIOTHERAPY; IRRADIATION; THERAPY; SYSTEM; STRESS; SIZE;
D O I
10.2217/nnm-2018-0171
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: To identify new mechanisms responsible for the radiosensitization effect of gold nanoparticles (GNPs). Materials & methods: A549 lung carcinoma cells were incubated with 10-nm GNPs during 6 or 24 h before to be exposed to 25 keV/mu m protons or 225 kV x-rays. Results: GNP incubation led to a time-dependent mitochondria membrane depolarization, oxidative stress and to x-ray and proton radiosensitization. Moreover, a marked inhibition of thioredoxin reductase was observed. Irradiation of cells invalidated for thioredoxin reductase evidenced a radiosensitization effect, suggesting that this enzyme is a potential GNP target. Conclusion: We suggest that GNPs play a radiosensitizer role by weakening detoxification systems. Altogether, these results open up promising novel strategies for the development of nanotechnologies associated to radiotherapy.
引用
收藏
页码:2917 / 2937
页数:21
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