Hau Herman, Khanal Dipesh, Rogers Linda, Suchowerska Natalka, Kumar Rajiv, Sridhar Srinivas, McKenzie David, Chrzanowski Wojciech
Faculty of Pharmacy The University of Sydney New South Wales 2006 Sydney, Australia.
Chris O'Brien Lifehouse Sydney New South Wales 2006 Sydney, Australia.
Bioeng Transl Med. 2016 May 27;1(1):94-102. doi: 10.1002/btm2.10007. eCollection 2016 Mar.
Despite major advances in the field of radiotherapy, healthy tissue damage continues to constrain the dose that can be prescribed in cancer therapy. Gold nanoparticles (GNPs) have been proposed as a solution to minimize radiation-associated toxicities by enhancing the radiation dose delivered locally to tumor cells. In the current study, we investigated the application of third-generation GNPs in two-dimensional (2D) and three-dimensional (3D) cell cultures and whether there is synergy between the nanoparticles and kilo- or mega-voltage radiation to cause augmented cytotoxicity. The 10-nm GNPs were found to be nontoxic in both 2D and 3D in vitro cultures of colon cancer cells at concentrations of up to 10-25 µg/ml. There was a significant increase in cell survival fraction reduction following exposure to 1 Gy of kilo-voltage (18.3%) and 2 Gy of mega-voltage (35.3%) radiation when the cells were incubated with 50 µg/ml of GNPs. The biocompatibility of the GNPs combined with their substantial synergy with radiation encourages further investigations into their application in targeted cancer treatment.
尽管放射治疗领域取得了重大进展,但健康组织损伤仍然限制了癌症治疗中可规定的剂量。金纳米颗粒(GNPs)已被提议作为一种解决方案,通过增强局部传递到肿瘤细胞的辐射剂量来最小化辐射相关毒性。在当前研究中,我们研究了第三代GNPs在二维(2D)和三维(3D)细胞培养中的应用,以及纳米颗粒与千伏或兆伏辐射之间是否存在协同作用以导致增强的细胞毒性。在浓度高达10-25μg/ml时,发现10纳米的GNPs在结肠癌细胞的2D和3D体外培养中均无毒。当细胞与50μg/ml的GNPs一起孵育时,暴露于1 Gy千伏(18.3%)和2 Gy兆伏(35.3%)辐射后,细胞存活分数降低显著增加。GNPs的生物相容性及其与辐射的显著协同作用鼓励进一步研究它们在靶向癌症治疗中的应用。