Chen Ming, Deng Guang, He Yu, Li Xiaoling, Liu Wei, Wang Wu, Zhou Zhiguo, Yang Hong, Yang Shiping
International Joint Laboratory on Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.
Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
ACS Appl Bio Mater. 2020 Jan 21;3(1):639-647. doi: 10.1021/acsabm.9b01006. Epub 2020 Jan 9.
Reactive oxygen species (ROS)-based tumor therapy is still challenging due to limited ROS-generating efficacy. Herein, we constructed heparin-conjugated Fe@FeO NPs (Fe@FeO@heparin, denoted as MNPs) as a peroxidase-mimicking nanozyme to generate ROS for tumor therapy through the combination of the ultrasound-stimulated Fenton reaction and the increased concentration of HO by β-lapachone (La) in a tumor. La was first intraperitoneally injected into mice and induced to generate a considerable quantity of HO through a specific tumor reaction, which was catalyzed by MNPs to produce highly hydroxyl radicals (•OH). Furthermore, the therapy efficacy for malignant tumors could significantly be enhanced by an ultrasonic stimulation. With the help of the increased amount of HO generated by La in the tumor and the enhanced peroxidase-mimicking activity of MNPs by ultrasound, MNPs manifest good therapeutic performance in a 4T1 xenograft model, which provides a strategy for enhanced nanozyme-mediated tumor therapy.
基于活性氧（ROS）的肿瘤治疗由于ROS生成效率有限，仍然具有挑战性。在此，我们构建了肝素共轭的Fe@FeO纳米颗粒（Fe@FeO@肝素，记为MNP）作为一种模拟过氧化物酶的纳米酶，通过超声刺激的芬顿反应和肿瘤中β-拉帕醌（La）使过氧化氢（H₂O₂）浓度增加的联合作用来产生ROS用于肿瘤治疗。首先将La腹腔注射到小鼠体内，并通过特定的肿瘤反应诱导产生大量H₂O₂，然后由MNP催化产生高浓度的羟基自由基（•OH）。此外，超声刺激可显著增强对恶性肿瘤的治疗效果。借助La在肿瘤中产生的H₂O₂量增加以及超声增强MNP的模拟过氧化物酶活性，MNP在4T1异种移植模型中表现出良好的治疗性能，这为增强纳米酶介导的肿瘤治疗提供了一种策略。
