Overcoming Radiation Resistance by Iron-Platinum Metal Alloy Nanoparticles in Human Copper Transport 1-Overexpressing Cancer Cells via Mitochondrial Disturbance

Tsung-Lin Tsai,1,2 Yu-Hsuan Lai,3,4 Helen HW Chen,1,2,4 Wu-Chou Su1,2 1Center of Applied Nanomedicine, National Cheng Kung University, Tainan, 701, Taiwan; 2Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 3Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 4Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, TaiwanCorrespondence: Wu-Chou Su Rm. 6065, 6F., No. 35, Xiaodong Road, North Dist., Tainan, 704, TaiwanTel +886-6-2353535#3120Fax +886-6-2084112Email sunnysu@mail.ncku.edu.twHelen HW Chen No. 138, Sheng Li Road, North Dist., Tainan, 704, TaiwanTel +886-6-2353535#2461Fax +886-6-2359333Email helen@mail.ncku.edu.twBackground: Radiation therapy remains an important treatment modality in cancer therapy, however, resistance is a major problem for treatment failure. Elevated expression of glutathione is known to associate with radiation resistance. We used glutathione overexpressing small cell lung cancer cell lines, SR3A-13 and SR3A-14, established by transfection with γ-glutamylcysteine synthetase (γ-GCS) cDNA, as a model for investigating strategies of overcoming radiation resistance. These radiation-resistant cells exhibit upregulated human copper transporter 1 (hCtr1), which also transports cisplatin. This study was initiated to investigate the effect and the underlying mechanism of iron-platinum nanoparticles (FePt NPs) on radiation sensitization in cancer cells.Materials and Methods: Uptakes of FePt NPs in these cells were studied by plasma optical emission spectrometry and transmission electron microscopy. Effects of the combination of FePt NPs and ionizing radiation were investigated by colony formation assay and animal experiment. Intracellular reactive oxygen species (ROS) were assessed by using fluorescent