Glioma stem cells (GSCs), as a subpopulation of stem cell-like cells, have been proposed to play a crucial role in the progression of drug-resistance in glioblastoma (GBM). Therefore, the targeted eradication of GSCs can serve as a promising therapeutic strategy for the reversal of drug-resistance in GBM. Herein, the effects of silencing c-Myc and m-TOR on primary GBM cells extracted from patients were investigated. Results confirmed that dual inhibition treatment significantly (p < 0.05) and synergistically suppressed GSCs, and consequently reversed TMZ-resistance when compared with the single treatment group. Subsequently, to facilitate effective crossing of the BBB, a biological camouflaged cascade brain-targeting nanosystem (PMRT) was created. The PMRT significantly inhibited tumor growth and extended the lifespan of orthotopic transplantation TMZ-resistant GBM-grafted mice. Our data demonstrated that PMRT could precisely facilitate drug release at the tumor site across the BBB. Simultaneously, c-Myc and m-TOR could serve as synergistic targets to eradicate the GSCs and reverse GBM resistance to TMZ.

胶质瘤干细胞（GSC）作为干细胞样细胞的亚群，已被提出在胶质母细胞瘤（GBM）的耐药性发展中起关键作用。因此，有针对性地消灭GSCs可以作为逆转GBM耐药性的一种有前途的治疗策略。在本文中，研究了沉默c-Myc和m-TOR对从患者提取的原代GBM细胞的影响。结果证实，与单一治疗组相比，双重抑制治疗显着（p <0.05），并且协同抑制了GSC，因此逆转了TMZ耐药性。随后，为促进BBB的有效穿越，创建了生物伪装的级联脑靶向纳米系统（PMRT）。PMRT显着抑制肿瘤生长并延长了原位移植耐TMZ的GBM移植小鼠的寿命。我们的数据表明，PMRT可以精确促进药物在BBB肿瘤部位的释放。同时，c-Myc和m-TOR可以作为协同目标以根除GSC并逆转GBM对TMZ的抗性。