胶质瘤
脂质体
血脑屏障
药物输送
体内
转铁蛋白受体
化学
流式细胞术
靶向给药
癌症研究
药品
药理学
医学
内科学
转铁蛋白
生物
免疫学
生物化学
中枢神经系统
生物技术
有机化学
作者
Shuangming Kang,Wenjuan Duan,Shangqian Zhang,Dawei Chen,Jianfang Feng,Na Qi
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2020-01-01
卷期号:10 (10): 4308-4322
被引量:49
摘要
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.
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