Glioma is an aggressive malignant brain tumor with a very poor prognosis for survival. The poor tumor targeting efficiency and tumor microenvironment penetration barrier also as troubles inhibited the effective glioma chemotherapy. Here, we design a core-shell structure cascade amplified hybrid catalytic nanopotentiators CFpAD with DM1 encapsulated to overcome the glioma therapeutic obstacles. NIR laser-based BBB penetrating enhances the tumor accumulation of CFpAD. When CFpAD, as the cascade amplified drug, is treated on the cancer cells, the bomb-like CFpAD releases gold nanoparticles as glucose oxidase (GOx) and ferric oxide nanoparticles (FNPs) as peroxides (POx) after blasting, producing ROS via a cascade amplification for tumor cell apoptosis. Gold nanoparticles can rest CAFs and reduce ECM secretion, achieving deep penetration of CFpAD. Moreover, CFpAD also cuts off the nutritional supply of the tumor, reduces the pH value, and releases free radicals to destroy the cancer. The glioma cell viability was significantly decreased through DNA damage and ROS aggregation due to the DM1-based chemotherapy synergistically combined with interventional photothermal therapy (IPTT) and radiotherapy (RT). This domino cascade amplified loop, combined with starvation therapy with IPTT and RT, has good tumor penetration and outstanding antitumor efficacy, and is a promising glioma treatment system.

中文翻译：

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双级联放大混合纳米电位器用于神经胶质瘤联合介入治疗


神经胶质瘤是一种侵袭性恶性脑肿瘤，生存预后非常差。肿瘤靶向效率差和肿瘤微环境渗透障碍也成为抑制胶质瘤化疗有效的障碍。在这里，我们设计了一种封装有 DM1 的核壳结构级联放大混合催化纳米电位器 CFpAD，以克服神经胶质瘤的治疗障碍。基于近红外激光的 BBB 穿透增强了 CFpAD 的肿瘤积累。当CFpAD作为级联放大药物作用于癌细胞时，炸弹般的CFpAD在爆炸后以葡萄糖氧化酶（GOx）的形式释放金纳米颗粒，以过氧化物（POx）的形式释放氧化铁纳米颗粒（FNP），通过级联产生ROS放大肿瘤细胞凋亡。金纳米粒子可以使CAF休息并减少ECM分泌，实现CFpAD的深度渗透。而且，CFpAD还能切断肿瘤的营养供应，降低pH值，释放自由基来消灭癌症​​。由于基于 DM1 的化疗与介入光热疗法 (IPTT) 和放射疗法 (RT) 协同结合，神经胶质瘤细胞活力因 DNA 损伤和 ROS 聚集而显着降低。这种多米诺级联放大环，结合IPTT和RT的饥饿疗法，具有良好的肿瘤穿透性和突出的抗肿瘤功效，是一种有前途的胶质瘤治疗系统。