GSH-Depleted Nanozymes with Hyperthermia-Enhanced Dual Enzyme-Mimic Activities for Tumor Nanocatalytic Therapy
GSH-Depleted Nanozymes with Hyperthermia-Enhanced Dual Enzyme-Mimic Activities for Tumor Nanocatalytic Therapy
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DOI：
10.1002/adma.202002439
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发表时间：
2020-09-11
影响因子：
29.4
通讯作者：
Lin, Jun
中科院分区：
文献类型：
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作者：
Dong, Shuming;Dong, Yushan;Lin, Jun
纳米催化治疗是一种新兴的治疗多种恶性肿瘤的技术，它使用人工纳米级的酶模拟物(纳米酶)。然而，纳米酶在肿瘤微环境(TME)中的催化活性相对不足，限制了其在生物医学上的应用。本文采用树枝状介孔二氧化硅(Bi2S3@DMSN)包覆均匀的Bi2S3 S(3)纳米棒，然后将超小的CeO2纳米酶修饰到Bi2S3@DMSN的大介孔中，从而制备出一种多功能的细菌状聚乙二醇/Ce-Bi@DMSN纳米酶。这些纳米酶在酸性条件下表现出双重的模拟酶催化活性(模拟过氧化物酶和模拟过氧化氢酶)，可以调节TME，即同时提高氧化应激和缓解缺氧。此外，纳米酶还可以通过氧化还原反应有效地消耗过表达的谷胱甘肽。光热疗法(PTT)被引入以协同提高双重模拟酶的催化活性，并通过光热消除肿瘤中过表达的GSH。这是通过利用聚乙二醇/Ce-Bi@DMSN纳米酶在第二近红外(NIR-II)窗口中所需的光吸收来实现的。随后，活性氧(ROS)介导的治疗效率显着提高。因此，本研究为高温增强纳米酶多酶活性用于肿瘤消融的概念提供了证据。
Nanocatalytic therapy, using artificial nanoscale enzyme mimics (nanozymes), is an emerging technology for therapeutic treatment of various malignant tumors. However, the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME) restrains their biomedical applications. Here, a versatile and bacteria-like PEG/Ce-Bi@DMSN nanozyme is developed by coating uniform Bi(2)S(3)nanorods (NRs) with dendritic mesoporous silica (Bi2S3@DMSN) and then decorating ultrasmall ceria nanozymes into the large mesopores of Bi2S3@DMSN. The nanozymes exhibit dual enzyme-mimic catalytic activities (peroxidase-mimic and catalase-mimic) under acidic conditions that can regulate the TME, that is, simultaneously elevate oxidative stress and relieve hypoxia. In addition, the nanozymes can effectively consume the overexpressed glutathione (GSH) through redox reaction. Photothermal therapy (PTT) is introduced to synergistically improve the dual enzyme-mimicking catalytic activities and depletion of the overexpressed GSH in the tumors by photonic hyperthermia. This is achieved by taking advantage of the desirable light absorbance in the second near-infrared (NIR-II) window of the PEG/Ce-Bi@DMSN nanozymes. Subsequently the reactive oxygen species (ROS)-mediated therapeutic efficiency is significantly improved. Therefore, this study provides a proof of concept of hyperthermia-augmented multi-enzymatic activities of nanozymes for tumor ablation.