胶质瘤
多西紫杉醇
超顺磁性
癌症研究
适体
靶向给药
微乳液
药物输送
材料科学
化学
生物
医学
分子生物学
纳米技术
生物化学
内科学
化疗
物理
磁场
磁化
量子力学
肺表面活性物质
作者
Hong Wang,Wanghao Chen,Guojian Wu,Jun Kong,Shaofei Yuan,Lukui Chen
标识
DOI:10.1016/j.xphs.2021.03.018
摘要
Abstract
Glioma-targeted drug delivery is a hugely challenging task because of the multibarrier in the brain. In this study, we report a magnetic T7 peptide&AS1411 aptamer-modified microemulsion for triple glioma-targeted delivery of shikonin and docetaxel (Fe3O4@T7/AS1411/DTX&SKN-M). Such a system comprises two tumor-targeted ligands (T7 peptide and AS1411 aptamer), ultra-small superparamagnetic iron oxide nanoparticle (Fe3O4), and shikonin&docetaxel-coloaded microemulsion (SKN&DTX-M). Fe3O4@T7/AS1411/DTX&SKN-M is capable of stably circulating in the blood, accumulating around the brain under an external magnetic field, distributing inside the glioma via the affinity to nucleolin/transferrin receptor, and retarding the growth of orthotopic glioma. Fe3O4@T7/AS1411/DTX&SKN-M encapsulated Fe3O4 nanoparticles in the core to obtain the superparamagnetism, which did not influence the main surface properties. Introducing 6% (wt%) of DSPE-PEG2000-T7 and 180 nM of AS1411 collaboratively enhanced the murine glioma (G422) cellular uptake of Fe3O4@T7/AS1411/DTX&SKN-M and thereby achieved the strongest antiproliferation among all the groups. Notably, the drug distribution at the brain sites of orthotopic Luc-G422 glioma tumor-bearing nude mice treated with Fe3O4@T7/AS1411/DTX&SKN-M was overwhelming among all the treatments. Most importantly, Fe3O4@T7/AS1411/DTX&SKN-M not only significantly reduced the luminescence signal at the brain areas of orthotopic Luc-G422 glioma mice but also prolonged the overall survival period. The enhancement of anti-glioma efficacy was associated with down-regulating the population of CD133- and CD44-positive cells within the tumors. In summary, such a triple glioma-targeted delivery of shikonin and docetaxel using combinational magnetism and T7/AS1411 modification strategies provides a promising method for synergistic and precise glioma therapy.
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