A mechanistic study of gold nanoparticle radiosensitisation using targeted microbeam irradiation

被引：49

作者：

Ghita, Mihaela ^{[1
]}

McMahon, Stephen J. ^{[1
,2
,3
]}

Taggart, Laura E. ^{[1
]}

Butterworth, Karl T. ^{[1
]}

Schettino, Giuseppe ^{[4
]}

Prise, Kevin M. ^{[1
]}

机构：

[1] Queens Univ Belfast, Ctr Canc Res & Cell Biol, 97 Lisburn Rd, Belfast BT7 9AE, Antrim, North Ireland

[2] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA

[3] Harvard Med Sch, Boston, MA 02114 USA

[4] Natl Phys Lab, London TW11 0LW, England

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

X-RAY MICROBEAM; RADIATION; RADIOTHERAPY;

D O I：

10.1038/srep44752

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Gold nanoparticles (GNPs) have been demonstrated as effective radiosensitizing agents in a range of preclinical models using broad field sources of various energies. This study aimed to distinguish between these mechanisms by applying subcellular targeting using a soft X-ray microbeam in combination with GNPs. DNA damage and repair kinetics were determined following nuclear and cytoplasmic irradiation using a soft X-ray ( carbon K-shell, 278 eV) microbeam in MDA-MB-231 breast cancer and AG01522 fibroblast cells with and without GNPs. To investigate the mechanism of the GNP induced radiosensitization, GNP-induced mitochondrial depolarisation was quantified by TMRE staining, and levels of DNA damage were compared in cells with depolarised and functional mitochondria. Differential effects were observed following radiation exposure between the two cell lines. These findings were validated 24 hours after removal of GNPs by flow cytometry analysis of mitochondrial depolarisation. This study provides further evidence that GNP radiosensitisation is mediated by mitochondrial function and it is the first report applying a soft X-ray microbeam to study the radiobiological effects of GNPs to enable the separation of physical and biological effects.

引用

页数：12

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