Sun Ting, Wu Haibin, Li Yanyan, Huang Yulun, Yao Lin, Chen Xionghui, Han Xiaoxiao, Zhou Youxin, Du Ziwei
Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Emergency Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Oncotarget. 2017 Aug 10;8(43):74451-74465. doi: 10.18632/oncotarget.20165. eCollection 2017 Sep 26.
Glioma stem cells, which are sub-populations of tumor cells, are responsible for resistant responses to radiotherapy and chemotherapy after surgery. Targeting resistant glioma stem cell sub-populations might present a novel means to prevent tumor recurrence. Due to the high expression of transferrin receptors at the surface of brain capillary endothelial and tumor cells, especially glioma stem cells, targeting the transferrin receptor system provides an avenue for the entry of drug molecules into the brain. Nanoparticles that target glioma stem cell sub-populations, conjugate transferrin and encapsulate temozolomide, were developed as a potential therapeutic strategy to evaluate their effectiveness at damaging tumor cells. Nanoparticles were highly effective at penetrating the blood-brain barrier and delivering a high therapeutic dose of temozolomide. This effective means of delivery provoked enhanced cytotoxicity against glioma cells, and especially against glioma stem cells. The targeting transferrin receptor nanoparticles display an inherent capacity for a highly therapeutic approach in targeting glioma stem cells and non-stem cells tumors. In addition, transferrin nanoparticles encapsulating temozolomide have the potential of a promising anti-tumor strategy against glioma of the O6-methylguanine-DNA-methyltransferase gene promoter methylation.
胶质瘤干细胞是肿瘤细胞的亚群，负责手术后对放疗和化疗的抗性反应。靶向抗性胶质瘤干细胞亚群可能是预防肿瘤复发的一种新方法。由于脑毛细血管内皮细胞和肿瘤细胞表面，特别是胶质瘤干细胞表面转铁蛋白受体的高表达，靶向转铁蛋白受体系统为药物分子进入大脑提供了一条途径。开发了靶向胶质瘤干细胞亚群、结合转铁蛋白并包裹替莫唑胺的纳米颗粒，作为一种潜在的治疗策略来评估它们对肿瘤细胞的损伤效果。纳米颗粒在穿透血脑屏障和递送高治疗剂量的替莫唑胺方面非常有效。这种有效的递送方式增强了对胶质瘤细胞，尤其是对胶质瘤干细胞的细胞毒性。靶向转铁蛋白受体纳米颗粒在靶向胶质瘤干细胞和非干细胞肿瘤方面显示出固有的高治疗潜力。此外，包裹替莫唑胺的转铁蛋白纳米颗粒有可能成为针对O6-甲基鸟嘌呤-DNA-甲基转移酶基因启动子甲基化的胶质瘤的一种有前景的抗肿瘤策略。
