Angiopep-2 Modified Cationic Lipid-Poly-Lactic-Co-Glycolic Acid Delivery Temozolomide and DNA Repair Inhibitor Dbait to Achieve Synergetic Chemo-Radiotherapy Against Glioma.

The therapeutic treatment of glioblastoma multiforme (GBM) remains a major challenge. Synergistic chemotherapy and radiotherapy (RT) have been considered the standard clinical therapy for malignant glioma, but there are some outstanding problems. First, gliomas are deemed exceedingly radio-resistant tumors, owing to efficient DNA double-strand break repair. In addition, the first-line chemotherapeutic agent (temozolomide, TMZ) for glioma shows extensive side effects and low accumulation in brain tumors. Therefore, we designed and constructed an Angiopep-2 modified cationic lipid-Poly-lactic-co-glycolic acid (PLGA), Angiopep-2 (A2)/DSPE-PEG2000/DOTAP/PLGA (APDP), to transport TMZ and a DNA repair inhibitor (Dbait) into glioblastoma cells, achieving concomitant chemo-radiotherapy treatment of glioma. At the cellular level, the APDP+TMZ/Dbait can be well endocytosed and enhance accumulation of the agent in brain tumors. Furthermore, the nanoparticle combined with Dbait improves the efficiency of radiotherapy in GBM. Our experimental data demonstrate that APDP+TMZ/Dbait has great potential as a multipurpose nanomedicine for the synergistic chemo-radiotherapy and radio-sensitization of malignant glioma in precise medical applications.