2024-11-18 作者：wff 来源：文献：
Construction of Functional Targeting Daunorubicin Liposomes Used for Eliminating Brain Glioma and Glioma Stem Cells
文献链接：
https://pubmed.ncbi.nlm.nih.gov/29336535/
作者：
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
相关产品：
DSPE-PEG2000-NHS
原文摘要：
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.
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）和磷脂-聚乙二醇-葡萄糖（DSPE-PEG2000-GLU）修饰脂质体，合成功能靶向柔红霉素脂质体。功能靶向柔红霉素脂质体能够地跨血脑屏障转移，对小鼠脑Glioma和神经Glioma干细胞具有作用。
合成方法:以DSPE-PEG2000-NHS和GLU为原料，通过一步酰化反应合成了靶向分子偶联物DSPE-PEG2000-GLU。GLU和DSPE-PEG2000-NHS以1：1（mg/mg）的比例溶解在无水二甲基甲酰胺（DMF）中。然后在室温氩气保护下，在荧光气容器中连续搅拌48 h。将粗产物转移到再生纤维素透析管（分子截止点，2000）中，用去离子水透析48 h，以去除未偶联的GLU和DMF溶剂。残渣冻干得到粉末，在−20c下保存。在二甲亚砜-d6溶剂中（400mhz1hNMR，Bruker AVANCE III400I）对反应产物进行表征。由DSPE-PEG2000-NHS和PEI600通过一步酰化反应合成了DSPE-PEG2000-PEI600。PEI600和DSPE-PEG2000-NHS以1：1（mol/mol）的比例溶解在无水二甲基甲酰胺（DMF）中。然后在室温保护下连续搅拌溶液24 h。
图为：靶向分子偶联物的表征
1H NMR谱。彩色箭头表示识别化合物的质子。相同的颜色阴影区域代表相应质子的峰，如下：粉红色表示GLU上的芳香族氢；蓝色表示DSPE-PEG2000-NHS上的聚乙二醇。
功能靶向柔红霉素脂质体的作用机制与其特性有关：在血液系统中的长时间循环、跨血脑屏障的转运能力。该功能性药物制剂通过细胞浆和线粒体中的Apoptosis信号通路显示出直接的细胞Poison性作用和Apoptosis诱导作用，从而显示出抗Cancer效果。
