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.

中文翻译：

---

血脑屏障可穿透的硫醇化​​紫杉醇寡聚（对亚苯基亚乙烯基）纳米药物可提高胶质母细胞瘤治疗的药效

摘要 血脑屏障（BBB）阻塞和肿瘤细胞的耐药性严重降低了大多数化疗药物治疗胶质母细胞瘤（GBM）的效率。在这里，开发了一种含有 Angiopep-2 和紫杉醇 (PTX) 的硫醇化寡聚体（对亚苯基亚乙烯基）（Ang-OPV-PTX），具有 BBB 渗透能力和更高的药物效率，用于 GBM 治疗。Ang-OPV-PTX 可以在 Angiopep-2 的帮助下通过 LRP1 介导的内吞作用有效穿透 BBB。此外，GBM 细胞中高水平的活性氧 (ROS) 诱导 Ang-OPV-PTX 上的巯基交联，导致大量聚集体的形成，从而阻止药物从肿瘤细胞中流出并改善药物功效。而且，Ang-OPV-PTX 可以特异性靶向并定位于 GBM 中，在体内而非正常组织中发挥长期治疗作用。基于这些特点，Ang-OPV-PTX在GBM化疗的临床应用中具有巨大的潜力。