文献：Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy

文献链接：https://pubmed.ncbi.nlm.nih.gov/34130695/

作者：Weidong Fei , Yunchun Zhao , Xiaodong Wu , Dongli Sun , Yao Yao , Fengmei Wang , Meng Zhang, Chaoqun Li1, Jiale Qin and Caihong Zheng

相关产品：DSPE-PEG2k-COOH 磷脂-聚乙二醇2000-羧基

原文摘要：Gestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. ENT1 has a high afnity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG2k-Cy conjugation exhibited a synergistic therapeutic efect on choriocarcinoma. Finally, Cy-Lipo@MTX exerted an extremely powerful antichoriocarcinoma efect with fewer side efects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efciency target for the rational design of active targeting nanotherapeutics.

DSPE - PEG2k - COOH 是一种多功能的生物材料。DSPE赋予材料优良的生物相容性和自组装能力，能够在适宜条件下形成脂质体等纳米结构。PEG2k 增强了材料的水溶性，有效减少在体内循环过程中的非特异性吸附。COOH（羧基）基团使其具备了化学反应活性，可通过与其他含有氨基、羟基等活性基团的分子进行共价键连接，实现对材料的进一步功能化修饰。该材料用于tumor靶向Treatment 、基因传递以及生物成像等方面。 对于（ENT1）在绒毛膜cancer细胞（JEG-3）膜上的过表达，该文献研究引入阿糖胞苷（Cy，ENT1的底物）移植脂质体（Cy-Lipo）靶向传递甲氨蝶呤（Cy-Lipo@MTX）。过程如下：

图：(a)DSPE-PEG2k-Cy 的合成图，(b)Cy-Lipo-MTX的制备工艺，(c)Cy-Lipo@MTX用于绒毛膜cancer的示意图

脂质@MTX和Cy脂质@MTX的制备

将Te MTX粉末溶于氢氧化钠溶液中。用盐酸溶液将溶液的pH值调整至7.0-8.0。采用上述方法得到的均匀、稳定的MTX溶液制备了以下MTX配方。采用薄flm水化法和高压均质法制备Cy-Lipo@MTX。简而言之，将大豆磷脂、胆固醇和DSPE-PEG2k-Cy加入到圆底瓶中，用氯仿溶解。在旋转蒸发器上形成黄色flm。将圆底烧瓶放入真空干燥箱中过夜，以去除残留的氯仿。然后，将MTX溶液加入到圆底瓶中，水化。在此过程中，透明的黄色溶液逐渐变成了黄色的胶体溶液。将水合液体超声，用高压匀浆器匀浆次。采用超微化系统去除冗余游离化合物。最后，用甘露醇作为冷冻保护剂，冷冻干燥。Lipo@MTX的制备方法是用DSPE-PEG2k-COOH代替DSPE-PEG2k-Cy，其他制备方法如上所述。

图：在不同的pH值下释放Lipo@MTX和Cy-Lipo@MTX

结论：ENT1对Cy-Lipo具有很高的亲和力，DSPE-PEG2k-COOH参与制备的的纳米载体内吞进入JEG-3细胞。ENT1蛋白在内吞作用过程中通过循环和再生来维持其运输功能。因此，在生物分布研究中，cy脂制剂在生物分布研究中显示出高tumor积累。DSPE-PEG2k-Cy偶联对绒毛膜cancer表现出协同应用效果。最后，Cy-Lipo@MTX具有抗绒毛膜cancer作用。