State Key Laboratory of Rare Earth Resource Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry , Chinese Academy of Sciences , Changchun 130022 , P.R. China.
University of Chinese Academy of Sciences , Beijing 100039 , P.R. China.
ACS Nano. 2018 Oct 23;12(10):10201-10211. doi: 10.1021/acsnano.8b05200. Epub 2018 Oct 3.
Shutting down glucose supply by glucose oxidase (GOx) to starve tumors has been considered to be an attractive strategy in cancerous starvation therapy. Nevertheless, the in vivo applications of GOx-based starvation therapy are severely restricted by the poor GOx delivery efficiency and the self-limiting therapeutic effect. Herein, a biomimetic nanoreactor has been fabricated for starvation-activated cancer therapy by encapsulating GOx and prodrug tirapazamine (TPZ) in an erythrocyte membrane cloaked metal-organic framework (MOF) nanoparticle (TGZ@eM). The fabricated TGZ@eM nanoreactor can assist the delivery of GOx to tumor cells and then exhaust endogenous glucose and O to starve tumors efficiently. Importantly, the resulting tumor hypoxia by GOx-based starvation therapy further initiates the activation of TPZ, which is released from the nanoreactor in the acid lyso/endosome environment, for enhanced colon cancer therapy. More importantly, by integrating the biomimetic surface modification, the immunity-escaping and prolonged blood circulation characteristics endow our nanoreactor dramatically improved cancer targeting ability. The in vitro and in vivo outcomes indicate our biomimetic nanoreactor exhibits a strong synergistic cascade effect for colon cancer therapy in an accurate and facile manner.
通过葡萄糖氧化酶 (GOx) 切断葡萄糖供应以使肿瘤饥饿已被认为是癌症饥饿疗法中的一种有吸引力的策略。然而，基于 GOx 的饥饿疗法的体内应用受到 GOx 传递效率差和自限性治疗效果的严重限制。在此，通过将 GOx 和前药替拉扎明 (TPZ) 封装在红细胞膜包裹的金属有机骨架 (MOF) 纳米颗粒 (TGZ@eM) 中，构建了一种仿生纳米反应器用于饥饿激活的癌症治疗。所构建的 TGZ@eM 纳米反应器可以辅助 GOx 递送至肿瘤细胞，然后有效地耗尽内源性葡萄糖和 O2 以饿死肿瘤。重要的是，GOx 饥饿疗法引起的肿瘤缺氧进一步引发了 TPZ 的激活，TPZ 从纳米反应器在酸性溶酶体/内体环境中释放，从而增强了结肠癌的治疗效果。更重要的是，通过整合仿生表面修饰、免疫逃逸和延长血液循环的特性，使我们的纳米反应器具有显著提高的癌症靶向能力。体外和体内结果表明，我们的仿生纳米反应器以准确和简便的方式为结肠癌治疗表现出强烈的协同级联效应。
