Rationale: The dual-targeted drug delivery system was designed for enhancing permeation of the blood-brain barrier (BBB) and providing an anti-glioma effect. As transferrin receptor (TfR) is over-expressed by the brain capillary endothelial (hCMEC/D3) and glioma cells, a mouse monoclonal antibody, RI7217, with high affinity and selectivity for TfR, was used to study the brain targeted drug delivery system. Muscone, an ingredient of traditional Chinese medicine (TCM) musk, was used as the "guide" drug to probe the permeability of the BBB for drug delivery into the cerebrospinal fluid. This study investigated the combined effects of TCM aromatic resuscitation and modern receptor-targeted technology by the use of muscone/RI7217 co-modified docetaxel (DTX) liposomes for enhanced drug delivery to the brain for anti-glioma effect.

Methods: Cellular drug uptake from the formulations was determined using fluorescence microscopy and flow cytometry. The drug penetrating ability into tumor spheroids were visualized using confocal laser scanning microscopy (CLSM). In vivo glioma-targeting ability of formulations was evaluated using whole-body fluorescent imaging system. The survival curve study was performed to evaluate the anti-glioma effect of the formulations.

Results: The results showed that muscone and RI7217 co-modified DTX liposomes enhanced uptake into both hCMEC/D3 and U87-MG cells, increased penetration to the deep region of U87-MG tumor spheroids, improved brain targeting in vivo and prolonged survival time of nude mice bearing tumor.

Conclusion: Muscone and RI7217 co-modified DTX liposomes were found to show improved brain targeting and enhanced the efficacy of anti-glioma drug treatment in vivo.

基本原理：双目标药物递送系统旨在增强血脑屏障（BBB）的渗透并提供抗神经胶质瘤的作用。由于脑毛细血管内皮细胞（hCMEC / D3）和神经胶质瘤细胞过度表达了转铁蛋白受体（TfR），因此采用了对TfR具有高亲和力和选择性的小鼠单克隆抗体RI7217，来研究脑靶向药物递送系统。Muscone是中药（TCM）麝香的一种成分，被用作“引导”药物，以检测BBB的渗透性，以将其输送到脑脊髓液中。这项研究通过使用muscone / RI7217共修饰的多西他赛（DTX）脂质体来增强中药向大脑的抗神经胶质瘤作用的递送，研究了中药芳香复苏和现代受体靶向技术的联合作用。

方法：使用荧光显微镜和流式细胞术测定制剂中的细胞药物吸收。使用共聚焦激光扫描显微镜（CLSM）观察药物对肿瘤球体的穿透能力。使用全身荧光成像系统评估制剂的体内胶质瘤靶向能力。进行存活曲线研究以评估制剂的抗神经胶质瘤作用。

结果：结果表明，muscone和RI7217共修饰的DTX脂质体增强了对hCMEC / D3和U87-MG细胞的摄取，增加了对U87-MG肿瘤球体深部的渗透，改善了脑体内靶向性，并延长了其存活时间。荷瘤的裸鼠。

结论：发现Muscone和RI7217共修饰的DTX脂质体可改善脑靶向性，并增强体内抗神经胶质瘤药物的治疗效果。