超分子PEG-DNA二氧化碳纳米凝胶，用于通过级联反应协同放大化学动力学治疗
Supramolecular PEG-DNA-Ferrocene Nanogels for Synergistically Amplified Chemodynamic Therapy via Cascade Reactions
影响因子:5.40000
分区:化学1区 Top / 有机化学1区 高分子科学1区 生化与分子生物学2区
发表日期:2024 Nov 11
作者:
Zhengwei Yan, Zongze Duan, Simin Liu, Zhiyong Zhao
摘要
化学动力疗法（CDT）受到肿瘤微环境的限制，例如低浓度的过氧化氢（H2O2）。增加H2O2与CDT的治疗策略的结合可以协同增强治疗作用。此处是一种新型的超分子PEG-DNA特环原纳米凝胶，可以通过casacade反应开发代码剂葡萄糖氧化酶（GOX）和低氧诱使前药tirapazamine（TPZ）。 DNA纳米凝胶是可控制的，DNase I-反应性的，并且具有良好的生物相容性。在GOX的催化反应中，纳米凝胶中的氧气催化反应，药物TPZ和二循环的催化剂和H2O2产生诱导，分别接受了基于缺氧的反应和芬顿反应。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H2O2的级联反应和基于缺氧的级联反应显然增加了。这种级联分子超分子纳米平板为协同扩大CDT提供了有希望的治疗策略。
Abstract
Chemodynamic therapy (CDT) has been limited by the tumor microenvironment, such as the low concentration of hydrogen peroxide (H2O2). The combination of therapeutic strategies that increase H2O2 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 H2O2 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 H2O2-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.