Blood-brain-barrier penetrable thiolated paclitaxel-oligo (p-phenylene vinylene) nanomedicine with increased drug efficiency for glioblastoma treatment. (December 2020)

• Record Type: Journal Article
• Authors: Guo, Yuduo; Liu, Ronghua; Zhou, Lingyun; Zhao, Hao; Lv, Fengting; Liu, Libing; Huang, Yiming; Zhang, Hong-Wei; Yu, Chunjiang; Wang, Shu
• Is Part Of: Nano today. Volume 35(2020)
• Publication Date: 2020-12
• Subjects: Glioblastoma treatment -- Blood-brain barrier -- Nanomedicines -- Supramolecular chemotherapy; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2020.100969
• Languages: English
• ISSNs: 1748-0132

Abstract

Graphical abstract: A thiolated oligo (p-phenylenevinylene) (Ang-OPV-PTX) with blood-brain barrier penetration capacity bearing Angiopep-2 and paclitaxel is developed to increase drug efficiency for glioblastoma treatment. The high reactive oxygen species (ROS) level in glioblastoma cells induced the crosslinking of sulfhydryl groups on Ang-OPV-PTX, leading to the formation of bulk aggregates, which prevents the efflux of the drug from tumor cells, and improves drug efficacy. Ang-OPV-PTX can specifically target and locate in GBM for a long-term therapeutic effect in vivo rather than normal tissues. Highlights: Improving the efficiency of chemotherapeutic drugs in the treatment of glioblastoma. Developing new nanodrug with BBB penetration capacity and good drug efficiency. In situ assembly inside tumor cells to prevent the efflux of the drug from tumor cells and improves drug efficacy. Specific target and locate in glioblastoma rather than normal tissues. Providing first example of paclitaxel-based nanodrug for chemotherapy of glioblastoma. Abstract: Blood-brain barrier (BBB) obstruction and the drug resistance of tumor cells severely reduce the efficiency of most chemotherapeutic drugs in the treatment of glioblastoma (GBM). Here, a thiolated oligo ( p -phenylenevinylene) (Ang-OPV-PTX) bearing Angiopep-2 and paclitaxel (PTX) with BBB penetration capacity and increased drug efficiency is developed for GBM treatment. Ang-OPV-PTX can effectively penetrate the BBB through LRP1-mediated endocytosis with the help of Angiopep-2. In addition, the high level of reactive oxygen species (ROS) in GBM cells induces the crosslinking of sulfhydryl groups on Ang-OPV-PTX, leading to the formation of bulk aggregates, which prevents the efflux of the drug from tumor cells and improves drug efficacy. Moreover, Ang-OPV-PTX can specifically target and locate in GBM for a long-term therapeutic effect in vivo rather than normal tissues. Based on these characteristics, Ang-OPV-PTX has great potential in the clinical application of GBM chemotherapy.