School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001, China.
Biomater Sci. 2019 Aug 20;7(9):3683-3692. doi: 10.1039/c9bm00641a.
Synergistic cancer starvation/ROS-mediated/chemo-therapy is developed through a cascade reaction with enzyme glucose oxidase (GOX) modified on the surface of an Fe-based metal organic framework (MOF(Fe)) and drug camptothecin (CPT) loaded into the cavities of MOF(Fe). Once internalized by tumor cells, GOX catalyzes endogenous glucose into hydrogen peroxide (H2O2) and gluconic acid (H+) enabling starvation therapy through choking off energy (glucose) supply. Meanwhile, the acidic micro-environment of tumor enhanced by the generated H+ degrades the MOF(Fe) simultaneously releasing CPT for chemotherapy and Fe3+, catalyzing H2O2 into one of the strongest reactive oxygen species (ROS) ˙OH enabling ROS-mediated therapy. Both in vitro and in vivo results show remarkable tri-modal synergistic anticancer effects. This work may shed some light on the development of novel multi-modal cancer therapies without any external intervention.
通过在铁基金属有机骨架（MOF(Fe)）表面修饰酶葡萄糖氧化酶（GOX）并将药物喜树碱（CPT）载入 MOF(Fe)的腔中，开发了协同癌症饥饿/ROS 介导/化疗。一旦被肿瘤细胞内化，GOX 将内源性葡萄糖催化成过氧化氢（H2O2）和葡萄糖酸（H+），通过阻断能量（葡萄糖）供应来实现饥饿疗法。同时，由生成的 H+增强的肿瘤酸性微环境同时降解 MOF(Fe)，释放 CPT 进行化疗和 Fe3+，催化 H2O2 生成一种最强的活性氧（ROS）˙OH，从而实现 ROS 介导的治疗。体外和体内结果均显示出显著的三模式协同抗癌作用。这项工作可能为开发新型无需任何外部干预的多模式癌症治疗方法提供一些思路。
