Current chemotherapeutics for glioma are not sufficiently effective due to their low tolerance and poor blood–brain barrier (BBB) permeability. Energy restriction based on co-delivery of albendazole (Abz) and nano-silver has been proven to suppress tumor growth without adverse effects. Accordingly, menthol was conjugated to BSA (MeB) to overcome the BBB-permeability issue. In this study, Abz-loaded MeB-silver nanoparticles (MBS-Abz) were developed by self-assembly of MeB, albendazole and nano silver for glioma targeting therapy. The nanoparticle entered the brain across the BBB and specifically accumulated in the glioma region. MeB delivered the nanoparticles across the brain capillary endothelial cell monolayer by promoting internalization and BBB disruption. MBS-Abz hindered ATP generation via the inhibition of glycolytic and mitochondrial pathways both in vitro and in vivo. The anti-glioma mechanisms of energy restriction were related to the cytotoxicity, proliferation inhibition, cell cycle arrest, and apoptosis induced by ATP exhaustion, and the effects of MBS-Abz were significantly better than those induced by monotherapy nanoparticles or unmodified nanoparticles. These results demonstrated that by combining the energy restriction effect of albendazole and nano silver, as well as the BBB penetration ability of menthol, MBS-Abz achieves superior anti-glioma efficacy and can be an effective strategy for glioma therapy.

当前的神经胶质瘤化疗药物由于其低耐受性和差的血脑屏障（BBB）通透性而不够有效。已证明基于阿苯达唑（Abz）和纳米银的共同释放的能量限制可以抑制肿瘤生长，而不会产生不利影响。因此，将薄荷醇与BSA（MeB）结合以克服BBB的渗透性问题。在这项研究中，通过自组装MeB，阿苯达唑和纳米银的自组装开发了负载Abz的MeB-银纳米颗粒（MBS-Abz）用于神经胶质瘤靶向治疗。纳米粒子穿过血脑屏障进入大脑，并特别地积聚在神经胶质瘤区域。MeB通过促进内在化和BBB破坏，将纳米颗粒穿过脑毛细血管内皮细胞单层。MBS-Abz在体内外均通过抑制糖酵解和线粒体途径而阻碍了ATP的产生。能量限制的抗神经胶质瘤机制与ATP耗尽诱导的细胞毒性，增殖抑制，细胞周期停滞和凋亡有关，MBS-Abz的作用明显优于单药纳米颗粒或未经修饰的纳米颗粒诱导的神经胶质瘤。这些结果表明，通过结合阿苯达唑和纳米银的能量限制作用以及薄荷醇的BBB渗透能力，MBS-Abz可获得优异的抗神经胶质瘤功效，并且可以成为治疗神经胶质瘤的有效策略。ATP耗竭引起的细胞凋亡和凋亡，MBS-Abz的作用明显优于单药纳米颗粒或未经修饰的纳米颗粒。这些结果表明，通过结合阿苯达唑和纳米银的能量限制作用以及薄荷醇的BBB渗透能力，MBS-Abz可获得优异的抗神经胶质瘤功效，并且可以成为治疗神经胶质瘤的有效策略。ATP耗竭引起的细胞凋亡和凋亡，MBS-Abz的作用明显优于单药纳米颗粒或未修饰的纳米颗粒。这些结果表明，通过结合阿苯达唑和纳米银的能量限制作用以及薄荷醇的BBB渗透能力，MBS-Abz可获得优异的抗神经胶质瘤功效，并且可以成为治疗神经胶质瘤的有效策略。