Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors.
Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors.
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通过纳米酶自组装的仿生纳米花诱导细胞内氧化损伤对抗缺氧肿瘤
DOI：
10.1038/s41467-018-05798-x
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发表时间：
2018-08-20
影响因子：
16.6
通讯作者：
Qu X
中科院分区：
文献类型：
--
作者：
Wang Z;Zhang Y;Ju E;Liu Z;Cao F;Chen Z;Ren J;Qu X
活性氧簇(ROS)诱导的细胞凋亡是治疗恶性肿瘤的一种很有前途的策略。然而，目前的系统高度依赖于氧状态和/或外部刺激来产生ROS，这极大地限制了它们的治疗效果，特别是在缺氧肿瘤中。在这里，我们开发了一种基于纳米酶自组装的仿生纳米花，它可以在常氧和低氧条件下催化一系列细胞内生化反应来产生ROS，而不需要任何外部刺激。在我们的配方中，首先合成了PtCo纳米粒子，并将其用于指导MnO2的生长。通过调节反应物的配比，得到了高度有序的MnO2@PtCo纳米花，其中PtCo具有模拟氧化物酶的功能，而MnO2具有模拟过氧化氢酶的功能，具有良好的催化效率。这样，定义良好的MnO2@PtCo纳米花不仅可以缓解缺氧状态，而且可以通过ROS介导的机制显著诱导细胞凋亡，从而显著而特异地抑制肿瘤生长。
Reactive oxygen species (ROS)-induced apoptosis is a promising treatment strategy for malignant neoplasms. However, current systems are highly dependent on oxygen status and/or external stimuli to generate ROS, which greatly limit their therapeutic efficacy particularly in hypoxic tumors. Herein, we develop a biomimetic nanoflower based on self-assembly of nanozymes that can catalyze a cascade of intracellular biochemical reactions to produce ROS in both normoxic and hypoxic conditions without any external stimuli. In our formulation, PtCo nanoparticles are firstly synthesized and used to direct the growth of MnO2. By adjusting the ratio of reactants, highly-ordered MnO2@PtCo nanoflowers with excellent catalytic efficiency are obtained, where PtCo behaves as oxidase mimic and MnO2functions as catalase mimic. In this way, the well-defined MnO2@PtCo nanoflowers not only can relieve hypoxic condition but also induce cell apoptosis significantly through ROS-mediated mechanism, thereby resulting in remarkable and specific inhibition of tumor growth.