Zhao Wei-Yu, Zhang Cheng-Xiang, Liu Lei, Mu Li-Min, Zeng Fan, Ju Rui-Jun, Xie Hong-Jun, Yan Yan, Zhao Yao, Lu Wan-Liang
J Biomed Nanotechnol. 2016 Jul;12(7):1404-420. doi: 10.1166/jbn.2016.2266.
The highly infiltrative nature of brain glioma makes total surgical removal of cancerous cells virtually impossible. Regular chemotherapy plays an important role in eradicating the residual cancer cells but is ineffective in treating brain glioma due to the hindrance of drug penetration into the tumor site by the blood brain barrier (BBB) and the regeneration of cancer cells by glioma stem cells (GSCs). In this study, functional targeting daunorubicin liposomes were developed by modifying the liposomes with distearoylphosphatidylethanolamine polyethylene glycol-polyethylenimine (DSPE-PEG2000PEI600 and a lipid-glucose derivative (DSPE-PEG2000-GLU). The studies were performed in brain glioma and glioma stem cells in vitro and in brain glioma-bearing mice inoculated with the glioma stem cells. The results showed that the functional targeting daunorubicin liposomes were able to significantly transfer across the BBB and exhibited an obvious efficacy in killing glioma and glioma stem cells in mice. The action mechanisms of the functional targeting daunorubicin liposomes were related to their properties: long-duration circulation in the blood system, transport capability across the BBB, concentrated accumulation in the brain glioma site, and increased internalization by malignant cells and their mitochondria. This functional drug formulation showed anticancer efficacy through a direct cytotoxic effect and an apoptosis-inducing effect through the apoptotic signaling pathways in the cytoplasm and mitochondria of the cells. As a chemotherapy strategy for treating brain glioma, functional targeting daunorubicin liposomes have the potential to eliminate brain glioma along with glioma stem cells.
脑胶质瘤具有高度浸润性，这使得彻底手术切除癌细胞几乎不可能。常规化疗在清除残留癌细胞方面发挥着重要作用，但由于血脑屏障（BBB）阻碍药物渗透到肿瘤部位以及胶质瘤干细胞（GSCs）促使癌细胞再生，常规化疗对脑胶质瘤的治疗效果不佳。在本研究中，通过用二硬脂酰磷脂酰乙醇胺聚乙二醇 - 聚乙烯亚胺（DSPE - PEG2000 - PEI600）和脂质 - 葡萄糖衍生物（DSPE - PEG2000 - GLU）修饰脂质体，制备了具有功能靶向性的柔红霉素脂质体。研究在脑胶质瘤细胞和胶质瘤干细胞的体外模型以及接种了胶质瘤干细胞的荷脑胶质瘤小鼠体内进行。结果表明，具有功能靶向性的柔红霉素脂质体能够显著穿过血脑屏障，并在杀死小鼠体内的胶质瘤细胞和胶质瘤干细胞方面表现出明显的效果。具有功能靶向性的柔红霉素脂质体的作用机制与其特性相关：在血液系统中循环时间长、具有穿过血脑屏障的运输能力、在脑胶质瘤部位集中积累以及被恶性细胞及其线粒体摄取增加。这种功能性药物制剂通过直接细胞毒性作用以及通过细胞胞质和线粒体中的凋亡信号通路诱导凋亡的作用来显示抗癌效果。作为一种治疗脑胶质瘤的化疗策略，具有功能靶向性的柔红霉素脂质体有潜力消除脑胶质瘤以及胶质瘤干细胞。
