Rezaee Zohre, Yadollahpour Ali, Bayati Vahid, Negad Dehbashi Fereshteh
Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Avhaz, Iran; Department of Medical Physics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Avhaz, Iran.
Int J Nanomedicine. 2017 Feb 21;12:1431-1439. doi: 10.2147/IJN.S128996. eCollection 2017.
Radiation therapy (RT) is the gold standard treatment for more than half of known tumors. Despite recent improvements in RT efficiency, the side effects of ionizing radiation (IR) in normal tissues are a dose-limiting factor that restricts higher doses in tumor treatment. One approach to enhance the efficiency of RT is the application of radiosensitizers to selectively increase the dose at the tumor site. Gold nanoparticles (GNPs) and electroporation (EP) have shown good potential as radiosensitizers for RT. This study aims to investigate the sensitizing effects of EP, GNPs, and combined GNPs-EP on the dose enhancement factor (DEF) for 6 MV photon energy.
Radiosensitizing effects of EP, GNPs, and combinations of GNPs-EP were comparatively investigated in vitro for intestinal colon cancer (HT-29) and Chinese hamster ovary (CHO) cell lines by MTT assay and colony formation assay at 6 MV photon energy in six groups: IR (control group), GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR.
Treatment of both cell lines with EP, GNPs, and combined GNPs-EP significantly enhanced the response of cells to irradiation. However, the HT-29 showed higher DEF values for all groups. In addition, the DEF value for HT-29 cells for GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR was, respectively, 1.17, 1.47, 1.36, 2.61, and 2.89, indicating synergistic radiosensitizing effect for the GNPs (24 h)+EP+IR group. Furthermore, the synergistic effect was observed just for HT-29 tumor cell lines.
Combined GNPs-EP protocols induced synergistic radiosensitizing effect in HT-29 cells, and the effect is also tumor specific. This combined therapy can be beneficially used for the treatment of intrinsically less radiosensitive tumors.
放射治疗(RT)是半数以上已知肿瘤的金标准治疗方法。尽管近年来放疗效率有所提高,但正常组织中电离辐射(IR)的副作用仍是限制肿瘤治疗中提高剂量的剂量限制因素。提高放疗效率的一种方法是应用放射增敏剂来选择性地增加肿瘤部位的剂量。金纳米颗粒(GNPs)和电穿孔(EP)已显示出作为放疗放射增敏剂的良好潜力。本研究旨在研究EP、GNPs以及GNPs-EP联合应用对6 MV光子能量的剂量增强因子(DEF)的增敏作用。
采用MTT法和集落形成试验,在6 MV光子能量下,对六组肠道结肠癌细胞(HT-29)和中国仓鼠卵巢细胞(CHO)进行体外实验,比较EP、GNPs以及GNPs-EP联合应用的放射增敏效果,六组分别为:IR(对照组)、GNPs+IR、GNPs(24小时)+IR、EP+IR、GNPs+EP+IR以及GNPs(24小时)+EP+IR。
用EP、GNPs以及GNPs-EP联合处理两种细胞系均显著增强了细胞对辐射的反应。然而,HT-29在所有组中显示出更高的DEF值。此外,HT-29细胞对于GNPs+IR、GNPs(24小时)+IR、EP+IR、GNPs+EP+IR以及GNPs(24小时)+EP+IR的DEF值分别为1.17、1.47、1.36、2.61和2.89,表明GNPs(24小时)+EP+IR组具有协同放射增敏作用。此外,仅在HT-29肿瘤细胞系中观察到协同效应。
GNPs-EP联合方案在HT-29细胞中诱导了协同放射增敏作用,且该效应具有肿瘤特异性。这种联合治疗可有益地用于治疗本质上放射敏感性较低的肿瘤。