Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, China.
Institute of Advanced Materials and Nanotechnology, Wuhan University of Science and Technology, Wuhan 430081, China.
Biomacromolecules. 2024 Nov 11;25(11):7123-7133. doi: 10.1021/acs.biomac.4c00562. Epub 2024 Oct 14.
Chemodynamic therapy (CDT) has been limited by the tumor microenvironment, such as the low concentration of hydrogen peroxide (HO). The combination of therapeutic strategies that increase HO with CDT can synergistically enhance the therapeutic effect. Herein, a novel supramolecular PEG-DNA-ferrocene nanogel that can codeliver glucose oxidase (GOx) and the hypoxia-activable prodrug tirapazamine (TPZ) was developed to synergistically amplify CDT via cascade reactions. The DNA nanogel was size-controllable and DNase I-responsive and exhibited good biocompatibility. Induced by oxygen consumption and HO generation in the catalytic reaction of GOx, the drugs TPZ and ferrocene in the nanogel underwent the hypoxia-based reaction and the Fenton reaction, respectively. The vitro model tests, intracellular ROS test, MTT experiments, and DNA damage assay demonstrated that the HO-based cascade Fenton reaction and the hypoxia-based cascade reaction obviously increased ·OH generation and promoted the apoptosis of cancer cells. This cascade supramolecular nanoplatform provided a promising therapeutic strategy to synergistically amplify CDT.
化学动力学疗法（CDT）受到肿瘤微环境的限制，例如过氧化氢（HO）的浓度低。将增加 HO 的治疗策略与 CDT 相结合可以协同增强治疗效果。本文开发了一种新型超分子 PEG-DNA-二茂铁纳米凝胶，可共递送葡萄糖氧化酶（GOx）和缺氧激活前药替拉扎胺（TPZ），通过级联反应协同放大 CDT。DNA 纳米凝胶具有尺寸可控性和 DNase I 响应性，表现出良好的生物相容性。在 GOx 催化反应中耗氧和产生 HO 的诱导下，纳米凝胶中的药物 TPZ 和二茂铁分别经历了基于缺氧的反应和 Fenton 反应。体外模型测试、细胞内 ROS 测试、MTT 实验和 DNA 损伤测定表明，基于 HO 的级联 Fenton 反应和基于缺氧的级联反应明显增加了·OH 的生成，并促进了癌细胞的凋亡。这种级联超分子纳米平台为协同放大 CDT 提供了一种有前途的治疗策略。
