Despite advances in glioblastoma (GBM) treatments, current approaches have failed to improve the overall survival of patients. The oncogene BMI-1, a core member of the polycomb group proteins, is a potential novel therapeutic target for GBM. To enhance the efficacy and reduce the toxicity, PTC209, a BMI-1 inhibitor, was loaded into a PLGA–PEG nanoparticle conjugated with CD133 antibody (Nano-PTC209) and its effect on the behavior of human GBM stem-like cells (GSCs) and the human glioblastoma cell line (U87MG) was assessed. Nano-PTC209 has a diameter of ~ 75 nm with efficient drug loading and controlled release. The IC50 values of Nano-PTC209 for GSCs and U87MG cells were considerably lower than PTC209. Nano-PTC209 significantly decreased the viability of both GSCs and U87MG cells in a dose-dependent manner and caused a significant enhancement of apoptosis and p53 levels as well as inhibition of AKT and JNK signaling pathways. Furthermore, Nano-PTC209 significantly inhibited the migration ability, decreased the activity of metalloproteinase-2 and -9, and increased the generation of reactive oxygen species in both GSCs and U87MG cells. Our data indicate that PLGA–PEG nanoparticle conjugated with CD133 antibody could be an ideal nanocarrier to deliver PTC209 and effectively target BMI-1 for potential approaches in the treatment of GBM.

中文翻译：

---

用含PLGA–PEG纳米颗粒的PTC209靶向BMI-1可调节人胶质母细胞瘤干细胞和癌细胞的行为

尽管胶质母细胞瘤（GBM）治疗取得了进展，但目前的方法未能改善患者的整体生存率。癌基因BMI-1是多梳基团蛋白的核心成员，是GBM的潜在新型治疗靶标。为了增强功效并降低毒性，将BMI-1抑制剂PTC209装入与CD133抗体（Nano-PTC209）偶联的PLGA-PEG纳米颗粒中，并且对人GBM干样细胞（GSC）的行为具有影响并评估了人胶质母细胞瘤细胞系（U87MG）。纳米PTC209的直径约为75 nm，具有有效的载药量和控释效果。对于GSC和U87MG电池，Nano-PTC209的IC50值明显低于PTC209。纳米PTC209以剂量依赖性方式显着降低GSC和U87MG细胞的活力，并导致凋亡和p53水平显着增强，以及AKT和JNK信号通路的抑制。此外，纳米PTC209在GSC和U87MG细胞中均显着抑制迁移能力，降低了金属蛋白酶2和-9的活性，并增加了活性氧的生成。我们的数据表明，与CD133抗体缀合的PLGA-PEG纳米颗粒可能是理想的纳米载体，可提供PTC209并有效靶向BMI-1，以治疗GBM。并增加了GSC和U87MG细胞中活性氧的产生。我们的数据表明，与CD133抗体缀合的PLGA-PEG纳米颗粒可能是理想的纳米载体，可提供PTC209并有效靶向BMI-1，以治疗GBM。并增加了GSC和U87MG细胞中活性氧的产生。我们的数据表明，与CD133抗体缀合的PLGA-PEG纳米颗粒可能是理想的纳米载体，可提供PTC209并有效靶向BMI-1，以治疗GBM。