文献：A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy

文献链接：https://pubmed.ncbi.nlm.nih.gov/25289086/

作者：JLI QIN1 , CHENG-ZHENG WANG1 , HUIJIE FAN2 , CHONGJIAN ZHANG1 ,HENGWEI ZHANG1 , MINHAO LV1 and SHUDE CUI

相关产品：DSPE-PEG2000-BTC

原文摘要：The treatment of a brain glioma remains one of the most difficult challenges in oncology. In the present study a delivery system was developed for targeted drug delivery across the bloodbrain barrier (BBB) to the brain cancer cells. A cyclic arginineglycineaspartic acid (RGD) peptide and transferrin (TF) were utilized as targeting ligands. Cyclic RGD peptides are specific targeting ligands of cancer cells and TFs are ligands that specifically target the BBB and cancer cells. Liposome (LP) was used to conjugate the cyclic RGD and TFs to establish the brain glioma cascade delivery system (RGD/TFLP). The LPs were prepared by the thin film hydration method and physicochemical characterization was conducted. In vitro cell uptake and threedimensional tumor spheroid penetration studies demonstrated that the system could target endothelial and tumor cells, as well as penetrate the tumor cells to reach the core of the tumor spheroids. The results of the in vivo imaging further demonstrated that the RGD/TFLP provided the highest brain distribution. As a result, the paclitaxelloaded RGD/TFLP presents the best antiproliferative activity against C6 cells and tumor spheroids. In conclusion, the RGD/TFLP may precisely target brain glioma, which may be valuable for glioma imaging and therapy.

DSPE-PEG2000-BTC这一化合物名称可能结合了DSPE（二硬脂酰磷脂酰乙醇胺）、PEG2000（聚乙二醇，分子量为2000）以及BTC（功能基团或化合物）。DSPE-PEG2000-BTC可以作为药物载体、纳米粒子制备的原料或用于改善生物材料的性能等，它在药物传递、纳米技术、生物医学工程等领域具有应用前景。DSPE-PEG2000-BTC的应用较广，比如DSPE-PEG2000-BTC在双靶向脂质体LPs结合靶向胶质tumor中有着应用。

图为：用醋酸铀酰负染的LPs的透射电镜图像

DSPE-PEG2000-BTC在LPs的制备中的应用：

RGD与DSPE-PEG2000-BTC在等渗HEPES缓冲液中结合，反应条件如下：温和搅拌。用薄层色谱法追踪反应，直到肽被完全消耗为止。该混合物随后被用水透析，并进行冻干。所得到的偶联物DSPE-PEG2000-RGD用于制备LPs，无需进一步纯化。采用薄膜水合法制备了RGD偶联LPs（RGD LP）。将SPC、Cho、DSPE-PEG2000和DSPE-PEG2000-RGD溶解在氯仿中。然后通过旋转蒸发去除氯仿，并在真空下过夜去除任何残留的有机溶剂。随后，将薄膜放入磷酸盐缓冲盐水中水合，然后在间歇性探针超声进行。

图为：不同LP配方对体外和体内细胞穿透的特性。

结论：RGD/TFLP与TFLP或RGD LP输送系统相比，该系统具有增强和准确的靶向效果。用TF修饰的LPs有助于穿透和改善胶质tumor的靶向性，而RGD则增强了tumor中细胞的摄取和积累。该系统可以同时靶向内皮细胞和tumor细胞，穿透内皮细胞单层和tumor球体到达tumor细胞团块的中心。与单靶点RGD-LP或TF-LP相比，靶向和穿透效应导致胶质tumor积累最高，导致最佳的成像效果。因此，与TF和RGD偶联的双靶向LP可能有潜力作为神经胶质tumor中的药物传递系统。