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缺氧条件下金纳米颗粒的细胞摄取、毒性及放射增敏作用

Gold nanoparticle cellular uptake, toxicity and radiosensitisation in hypoxic conditions.

作者信息

Jain Suneil, Coulter Jonathan A, Butterworth Karl T, Hounsell Alan R, McMahon Stephen J, Hyland Wendy B, Muir Mark F, Dickson Glenn R, Prise Kevin M, Currell Fred J, Hirst David G, O'Sullivan Joe M

机构信息

Centre for Cancer Research and Cell Biology, School of Medicine, Queen's University Belfast, United Kingdom.

Experimental Therapeutics Research Group, School of Pharmacy, Queen's University Belfast, United Kingdom.

出版信息

Radiother Oncol. 2014 Feb;110(2):342-7. doi: 10.1016/j.radonc.2013.12.013. Epub 2014 Jan 17.

Abstract

BACKGROUND AND PURPOSE

Gold nanoparticles (GNPs) are novel agents that have been shown to cause radiosensitisation in vitro and in vivo. Tumour hypoxia is associated with radiation resistance and reduced survival in cancer patients. The interaction of GNPs with cells in hypoxia is explored.

MATERIALS AND METHODS

GNP uptake, localization, toxicity and radiosensitisation were assessed in vitro under oxic and hypoxic conditions.

RESULTS

GNP cellular uptake was significantly lower under hypoxic than oxic conditions. A significant reduction in cell proliferation in hypoxic MDA-MB-231 breast cancer cells exposed to GNPs was observed. In these cells significant radiosensitisation occurred in normoxia and moderate hypoxia. However, in near anoxia no significant sensitisation occurred.

CONCLUSIONS

GNP uptake occurred in hypoxic conditions, causing radiosensitisation in moderate, but not extreme hypoxia in a breast cancer cell line. These findings may be important for the development of GNPs for cancer therapy.

摘要

背景与目的

金纳米颗粒(GNPs)是新型制剂,已证实在体外和体内均能引起放射增敏作用。肿瘤缺氧与癌症患者的放射抗性及生存率降低相关。本研究探讨了GNPs与缺氧条件下细胞的相互作用。

材料与方法

在有氧和缺氧条件下,于体外评估了金纳米颗粒的摄取、定位、毒性及放射增敏作用。

结果

缺氧条件下金纳米颗粒的细胞摄取显著低于有氧条件。观察到暴露于金纳米颗粒的缺氧MDA-MB-231乳腺癌细胞的细胞增殖显著降低。在这些细胞中,常氧和中度缺氧条件下均发生了显著的放射增敏作用。然而,在接近无氧条件下未发生显著增敏作用。

结论

在缺氧条件下会发生金纳米颗粒摄取,在乳腺癌细胞系的中度而非极端缺氧条件下引起放射增敏作用。这些发现可能对开发用于癌症治疗的金纳米颗粒具有重要意义。

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