Nanoscience Centre, Department of Engineering, University of Cambridge, Cambridge CB3 0FF, UK.
Nanoscale. 2014 Sep 21;6(18):10865-73. doi: 10.1039/c4nr03693j. Epub 2014 Aug 13.
Glioblastoma multiforme (GBM) remains the most aggressive and challenging brain tumour to treat. We report the first successful chemo-radiotherapy on patient derived treatment resistant GBM cells using a cisplatin-tethered gold nanosphere. After intracellular uptake, the nanosphere effects DNA damage which initiates caspase-mediated apoptosis in those cells. In the presence of radiation, both gold and platinum of cisplatin, serve as high atomic number radiosensitizers leading to the emission of ionizing photoelectrons and Auger electrons. This resulted in enhanced synergy between cisplatin and radiotherapy mediated cytotoxicity, and photo/Auger electron mediated radiosensitisation leading to complete ablation of the tumour cells in an in vitro model system. This study demonstrates the potential of designed nanoparticles to target aggressive cancers in the patient derived cell lines providing a platform to move towards treatment strategies.
多形性胶质母细胞瘤（GBM）仍然是治疗中最具侵袭性和挑战性的脑肿瘤。我们报告了首例使用顺铂连接的金纳米球对患者来源的治疗耐药 GBM 细胞进行成功的化疗-放疗。进入细胞内后，纳米球会导致 DNA 损伤，从而引发细胞中的半胱天冬酶介导的细胞凋亡。在辐射存在的情况下，顺铂的金和铂都充当高原子序数放射增敏剂，导致产生电离光电子和俄歇电子。这导致顺铂和放射治疗介导的细胞毒性之间的协同作用增强，以及光/俄歇电子介导的放射增敏作用增强，导致在体外模型系统中完全消融肿瘤细胞。这项研究证明了设计的纳米粒子靶向患者来源的细胞系中侵袭性癌症的潜力，为治疗策略的发展提供了一个平台。
