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.
Published Version
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