State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, Nankai University, Tianjin 300071, China.
National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
ACS Appl Mater Interfaces. 2021 Aug 11;13(31):37713-37723. doi: 10.1021/acsami.1c10816. Epub 2021 Aug 3.
Chemodynamic therapy (CDT) was regarded as a promising approach for tumor treatment. However, owing to the insufficient amount of endogenous hydrogen peroxide (HO) in tumor cells, the efficacy of CDT was limited. In this study, we designed phosphate-responsive nanoparticles (denoted as MGDFT NPs) based on metal-organic frameworks, which were simultaneously loaded with drug doxorubicin (DOX) and glucose oxidases (GOx). The decorated GOx could act as a catalytic nanomedicine for the response to the abundant glucose in the tumor microenvironment, generating a great deal of HO, which would enhance the Fenton reaction and produce toxic hydroxyl radicals (·OH). Meanwhile, the growth of tumors would also be inhibited by overconsuming the intratumoral glucose, which was the "fuel" for cell proliferation. When the nanoparticles entered into tumor cells, a high concentration of phosphate induced structure collapse, releasing the loaded DOX for chemotherapy. Furthermore, the decoration of target agents endowed the nanoparticles with favorable target ability to specific tumor cells and mitochondria. Consequently, the designed MGDFT NPs displayed desirable synergistic therapeutic effects via combining chemotherapy, starvation therapy, and enhanced Fenton reaction, facilitating the development of multimodal precise antitumor therapy.
化学动力学疗法（CDT）被认为是一种很有前途的肿瘤治疗方法。然而，由于肿瘤细胞内源性过氧化氢（HO）的含量不足，CDT 的疗效受到限制。在这项研究中，我们设计了基于金属有机框架的磷酸响应纳米粒子（记为 MGDFT NPs），其同时负载了药物阿霉素（DOX）和葡萄糖氧化酶（GOx）。修饰的 GOx 可以作为一种催化纳米药物，对肿瘤微环境中丰富的葡萄糖做出响应，产生大量的 HO，从而增强 Fenton 反应并产生有毒的羟自由基（·OH）。同时，肿瘤的生长也会受到过度消耗肿瘤内葡萄糖的抑制，葡萄糖是细胞增殖的“燃料”。当纳米粒子进入肿瘤细胞时，高浓度的磷酸诱导结构崩溃，释放负载的 DOX 进行化疗。此外，靶向剂的修饰使纳米粒子具有对特定肿瘤细胞和线粒体的良好靶向能力。因此，设计的 MGDFT NPs 通过结合化疗、饥饿疗法和增强的 Fenton 反应，表现出理想的协同治疗效果，有利于发展多模式精确抗肿瘤治疗。
