Tumor Microenvironment-Responsive and Catalytic Cascade-Enhanced Nanocomposite for Tumor Thermal Ablation Synergizing with Chemodynamic and Chemotherapy,ACS Applied Bio Materials

当前位置： X-MOL 学术 › ACS Appl. Bio Mater. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Tumor Microenvironment-Responsive and Catalytic Cascade-Enhanced Nanocomposite for Tumor Thermal Ablation Synergizing with Chemodynamic and Chemotherapy
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-04-27 , DOI: 10.1021/acsabm.0c00042
Ye Zhang ₁ , Yi Cao ₁ , Tian Gao ₁ , Ye Kuang ₂ , Zhen An ₁ , Zheng Mao ₁ , Yilin He ₁ , Jincong Yan ₁ , Zhongzhong Lu ₁ , Renjun Pei ₁

Affiliation

Chemodynamic therapy (CDT) is considered as a promising nanocatalytic therapeutic strategy for cancer because of its specific response toward the tumor microenvironment (TME). Improving the efficiency of this kind of reactive oxygen species (ROS)-mediated therapy is still a formidable challenge. Herein, we integrate CDT with other therapeutic methods together to enhance anticancer effects via overcoming robust ROS defensive mechanisms and hypoxia in cancer cells. The biocompatible and biodegraded nanoplatform (HMnO₂-DOX-GOD-HA) has been constructed on the basis of hollow MnO₂ nanoparticles loaded with chemotherapeutics doxorubicin (DOX) and glucose oxide (GOD) and further decorated with hyaluronic acid (HA) for targeting tumor cells. We demonstrated that HMnO₂-DOX-GOD-HA is not only able to deplete glutathione (GSH) to disturb the redox balance but also release Mn²⁺ to initiate the magnetic resonance imaging signal and induce Fenton reaction happening. Meanwhile, GOD-induced glucose oxidation and HMnO₂-catalyzed O₂ generation facilitate hypoxia relief and enhance toxic hydroxyl radical (•OH) production for CDT efficiency promotion. Upon 808 nm laser irradiation, cancer-killing efficiency can be notably increased by photothermally enhanced ion and drug release and thermal ablation. This work offers a paradigm to design a TME-responsive and imaging-guided synergistic strategy for hypoxia tumors based on GSH depletion and catalytic cascade-enhanced CDT, thermal ablation, and chemotherapy.

中文翻译：

肿瘤微环境响应和催化级联增强纳米复合材料与化学动力学和化学疗法协同用于肿瘤热消融

化学动力学疗法（CDT）因其对肿瘤微环境（TME）的特异性反应而被认为是一种很有前途的癌症纳米催化治疗策略。提高这种活性氧 (ROS) 介导的治疗的效率仍然是一项艰巨的挑战。在此，我们将 CDT 与其他治疗方法相结合，通过克服癌细胞中强大的 ROS 防御机制和缺氧来增强抗癌作用。生物相容和可生物降解的纳米平台（HMnO _{2 -DOX-GOD-HA）是在空心MnO}₂纳米粒子的基础上构建的，该纳米粒子负载有化疗药物阿霉素（DOX）和葡萄糖氧化物（GOD），并进一步用透明质酸（HA）修饰用于靶向肿瘤细胞。我们证明了 HMnO₂ -DOX-GOD-HA不仅能消耗谷胱甘肽(GSH)，扰乱氧化还原平衡，还能释放Mn ²⁺启动磁共振成像信号，诱发芬顿反应发生。同时，GOD 诱导的葡萄糖氧化和 HMnO ₂催化的 O ₂生成有助于缓解缺氧并增强有毒羟基自由基 (•OH) 的产生，从而提高 CDT 效率。在 808 nm 激光照射下，通过光热增强离子和药物释放以及热消融可以显着提高杀癌效率。这项工作为基于 GSH 耗竭和催化级联增强 CDT、热消融和化学疗法的缺氧肿瘤设计 TME 响应和成像引导的协同策略提供了一个范例。

更新日期：2020-04-27

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南