Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization , Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022 , P.R. China.
University of Science and Technology of China , Hefei , Anhui 230029 , P.R. China.
ACS Nano. 2019 May 28;13(5):5222-5230. doi: 10.1021/acsnano.8b09501. Epub 2019 Apr 23.
Metal-organic frameworks (MOFs)-based peroxidase mimics have been seldom applied in the biomedical field, especially in vivo. One of the main reasons is their optimum reactions occur in strong acidic environments with a pH of 3-4, severely limiting their applications in living systems where neutral pH is usually required. Other types of peroxidase mimics also suffer such a fatal defect. Additionally, the direct introduction of the relatively high concentrated and toxic reaction reagent HO would induce undesired damage to normal tissues. Herein, a MOF-based hybrid nanocatalyst as a benign and self-activated cascade reagent has been constructed. Owing to better catalytic performance compared with three-dimensional bulk MOF, an ultrathin two-dimensional (2D) MOF (2D Cu-TCPP(Fe)) nanosheet is chosen as a model of peroxidase mimic to physically adsorb glucose oxidase (GOx) for fabricating such a hybrid nanocatalyst. Nontoxic glucose can be continuously converted into abundant gluconic acid and HO by GOx, avoiding the direct use of relatively high concentrated and toxic HO and minimizing the harmful side effects. The generated gluconic acid can decrease the pH value from 7 to 3-4, dramatically activating the peroxidase-like activity of 2D Cu-TCPP(Fe) nanosheets. Meanwhile, the produced HO is used for subsequent catalysis of activated 2D Cu-TCPP(Fe) nanosheets, leading to efficient generation of an extremely toxic hydroxyl radial and antibacterial capacity. In vitro and in vivo results illustrate the designed benign and self-activated cascade reagent possesses a robust antibacterial effect with negligible biotoxicity.
基于金属-有机骨架（MOF）的过氧化物模拟物在生物医学领域，特别是在体内，很少得到应用。其中一个主要原因是它们的最佳反应发生在 pH 值为 3-4 的强酸性环境中，这严重限制了它们在中性 pH 值通常需要的活体系中的应用。其他类型的过氧化物模拟物也存在这样一个致命的缺陷。此外，相对高浓度和有毒的反应试剂 HO 的直接引入会对正常组织造成不必要的损伤。在此，构建了一种基于 MOF 的杂化纳米催化剂作为良性和自激活级联试剂。与三维块状 MOF 相比，由于具有更好的催化性能，选择超薄二维（2D）MOF（2D Cu-TCPP(Fe)）纳米片作为过氧化物模拟物的模型，物理吸附葡萄糖氧化酶（GOx）来制备这种杂化纳米催化剂。无毒的葡萄糖可以被 GOx 连续转化为丰富的葡萄糖酸和 HO，避免直接使用相对高浓度和有毒的 HO，并最大限度地减少有害的副作用。生成的葡萄糖酸可以将 pH 值从 7 降低到 3-4，显著激活 2D Cu-TCPP(Fe)纳米片的过氧化物样活性。同时，产生的 HO 用于随后催化激活的 2D Cu-TCPP(Fe)纳米片，导致极毒性羟基自由基的有效生成和抗菌能力。体外和体内结果表明，设计的良性和自激活级联试剂具有强大的抗菌效果，生物毒性可忽略不计。
