文献：Active targeting of orthotopic glioma using biomimetic liposomes co-loaded elemene and cabazitaxel modified by transferritin

文献链接：https://link.springer.com/article/10.1186/s12951-021-01048-3

作者：Jie Li, Huamin Zeng, Yu You, Rongrong Wang, Tiantian Tan, Weiming Wang, Liyan Yin, Zhaowu Zeng, Yiying Zeng , Tian Xie

相关产品：DSPE-PEG2000-transferrin（磷脂-聚乙二醇2000-转铁蛋白）

原文摘要：

Effective treatment of glioma requires a nanocarrier that can cross the blood–brain barrier (BBB) to target the tumor lesion. In the current study, elemene (ELE) and cabazitaxel (CTX) liposomes were prepared by conjugating liposomes with transferrin (Tf) and embedding the cell membrane proteins of RG2 glioma cells into liposomes (active-targeting biomimetic liposomes, Tf-ELE/CTX@BLIP), which exhibited effective BBB infiltration to target glioma. The findings showed that Tf-ELE/CTX@BLIP was highly stable. The liposomes exhibited highly significant homologous targeting and immune evasion in vitro and a 5.83-fold intake rate compared with classical liposome (ELE/CTX@LIP). Bioluminescence imaging showed increased drug accumulation in the brain and increased tumor penetration of Tf-ELE/CTX@BLIP in orthotopic glioma model nude mice. Findings from in vivo studies indicated that the antitumor effect of the Tf-ELE/CTX@BLIP led to increased survival time and decreased tumor volume in mice. The average tumor fluorescence intensity after intravenous administration of Tf-ELE/CTX@BLIP was 65.2, 12.5, 22.1, 6.6, 2.6, 1.5 times less compared with that of the control, CTX solution, ELE solution, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP groups, respectively. Histopathological analysis showed that Tf-ELE/CTX@BLIP were less toxic compared with administration of the CTX solution. These findings indicate that the active-targeting biomimetic liposome, Tf-ELE/CTX@BLIP, is a promising nanoplatform for delivery of drugs to gliomas.

DSPE-PEG2000-transferrin:磷脂-聚乙二醇2000-转铁蛋白。DSPE：1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺（DSPE）是一种磷脂。它具有亲脂性的长碳链脂肪酸（硬脂酸）部分，这使得它能够很好地插入脂质双层结构中。在这个分子结构中，磷酸乙醇胺部分提供了一个可以与其他分子连接的位点。PEG2000：聚乙二醇（PEG）部分的分子量为 2000。PEG 具有良好的亲水性和生物相容性，它就像一个 “桥梁” 连接着 DSPE 和转铁蛋白（transferrin）。PEG 链可以增加整个分子在水溶液中的稳定性，并且能够减少非特异性吸附，延长在体内循环系统中的滞留时间。Transferrin：转铁蛋白是一种血浆糖蛋白，主要功能是运输铁离子。它可以与细胞表面的转铁蛋白受体结合，通过受体 - 介导的内吞作用进入细胞。在这个复合物中，转铁蛋白赋予了分子靶向细胞的能力，特别是那些高表达转铁蛋白受体的细胞，如tumour细胞等。基于DSPE-PEG2000-transferrin的性能，脂质体Tf-ELE/CTX@BLIP的合成介绍如下：

图：流程示意

制备Tf-ELE/CTX@LIP：

将CTX溶解于乙醇中，超声浴下。然后加入 ELE、胆固醇、大豆卵磷脂、 TPGS、dspe - peg2000 -转铁蛋白和 MCT。将混合物加热并在水浴下溶解，形成油相。将甘油溶于水中，在一定温度下剪切，得到水相。将油相缓慢注入水相，剪切。然后使用超声超声器减小粒径。通过相同的工艺制备ELE/CTX@LIP，不添加DSPE-PEG2000-transferrin。采用直接挤压法制备cmp基脂质体。以Tf-ELE/CTX@LIP为基础生成Tf-ELE/CTX@BLIP，以ELE/CTX@LIP为基础生成ELE/CTX@BLIP。综上所述，将CMP与Tf-ELE/CTX@LIP或ELE/CTX@LIP以一定的磷脂与CMP重量比混合。通过孔直接挤压得到Tf-ELE/CTX@BLIP和ELE/CTX@BLIP。

图：表征图像

结论：

该文献成功制备出基于DSPE-PEG2000-transferrin合成的Tf-ELE/CTX@BLIP。结果表明，Tf-ELE/CTX@BLIP脂质体具有活性靶向作用、良好的同源识别和血脑屏障渗透能力，具有高度稳定性，组织病理学分析表明，与 CTX 溶液相比，Tf-ELE/CTX@BLIP 的poison性较小。