Chen Feng, Zhang Xiao Hong, Hu Xiao Dan, Zhang Wei, Lou Zhi Chao, Xie Li Hua, Liu Pei Dang, Zhang Hai Qian
College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, People's Republic of China.
Jiangsu Laboratory for Biomaterials and Devices, Southeast University, Nanjing, People's Republic of China.
Int J Nanomedicine. 2015 Aug 14;10:4957-69. doi: 10.2147/IJN.S82980. eCollection 2015.
Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.
放射治疗是癌症治疗的主要策略之一,但面临重大挑战,如癌细胞耐药性和对正常组织的辐射损伤。选择性提高癌细胞对辐射敏感性的放射增敏剂可增强放射治疗的效果。我们在此报告一种新型放射增敏剂的研发,该增敏剂由覆盖有抗癌药物新藤黄酸(NGA-CNPs)的单分散二氧化铈纳米颗粒(CNPs)组成。将其与辐射联合用于MCF-7乳腺癌细胞,并评估这种联合治疗方法的疗效和作用机制。NGA-CNPs增强了辐射的毒性作用,导致细胞死亡率高于单独使用任何一种治疗方法,并诱导自噬激活和细胞周期停滞在G2/M期,而用NGA或CNPs预处理并不能提高辐射诱导的癌细胞死亡率。然而,与其他纳米材料不同,NGA-CNPs减少了内源性和辐射诱导的活性氧生成。这些结果表明,辅助使用NGA-CNPs可通过降低杀死癌细胞所需的辐射剂量,从而将对健康邻近组织的附带损伤降至最低,提高乳腺癌放射治疗的效果。