Gadolinium-based nanoparticles as sensitizing agents to carbon ions in head and neck tumor cells.

Gadolinium-based nanoparticles as sensitizing agents to carbon ions in head and neck tumor cells.
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DOI:
10.1016/j.nano.2017.07.015
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发表时间:
2017-11
期刊:
Nanomedicine : nanotechnology, biology, and medicine
影响因子:
--
通讯作者:
A. Wozny;M. Aloy;Gersende Alphonse;N. Magné;M. Janier;O. Tillement;F. Lux;M. Beuve;C. Rodriguez-Lafras
A. Wozny;M. Aloy;Gersende Alphonse;N. Magné;M. Janier;O. Tillement;F. Lux;M. Beuve;C. Rodriguez-Lafras
中科院分区:
其他
文献类型:
--
作者:
A. Wozny;M. Aloy;Gersende Alphonse;N. Magné;M. Janier;O. Tillement;F. Lux;M. Beuve;C. Rodriguez-Lafras

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强子疗法的主要优点是改善肿瘤灭菌,同时由于碳离子的特定弹道(布拉格峰)而保护周围的健康组织。然而,它在大多数耐药癌症中的疗效仍然有限,例如III-IV级头颈部鳞状细胞癌(HNSCC),其中碳离子与钆基纳米颗粒(AGuIX®)的结合可用作特洛伊木马。我们首次报道了AGuIX®与碳离子辐射结合在人类肿瘤细胞中的放射增强作用。三种HNSCC细胞系(SQ 20 B、FaDu和Cal 33)中相对生物学有效性(1.7)的增加与杀死细胞所需的辐射剂量显著降低相关。放射增敏通过大量未修复的DNA双链断裂。这些结果强调了AGuIX®在使侵袭性肿瘤对强子疗法敏感方面的强大潜力,因此,在降低急性/晚期毒性的同时改善局部控制。
Hadrontherapy presents the major advantage of improving tumor sterilization while sparing surrounding healthy tissues because of the particular ballistic (Bragg peak) of carbon ions. However, its efficacy is still limited in the most resistant cancers, such as grade III-IV head and neck squamous cell carcinoma (HNSCC), in which the association of carbon ions with gadolinium-based nanoparticles (AGuIX®) could be used as a Trojan horse. We report for the first time the radioenhancing effect of AGuIX®when combined with carbon ion irradiation in human tumor cells. An increase in relative biological effectiveness (1.7) in three HNSCC cell lines (SQ20B, FaDu, and Cal33) was associated with a significant reduction in the radiation dose needed for killing cells. Radiosensitization goes through a higher number of unrepaired DNA double-strand breaks. These results underline the strong potential of AGuIX®in sensitizing aggressive tumors to hadrontherapy and, therefore, improving local control while lowering acute/late toxicity.