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一种基于 GSH 门控的 DNA 纳米器件用于肿瘤特异性 miRNA 的信号放大和 MRI 引导的治疗诊断。

A GSH-Gated DNA Nanodevice for Tumor-Specific Signal Amplification of microRNA and MR Imaging-Guided Theranostics.

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.

出版信息

Small. 2019 Oct;15(41):e1903016. doi: 10.1002/smll.201903016. Epub 2019 Aug 18.

Abstract

Developing tumor-responsive diagnosis and therapy strategies for tumor theranostics is still a challenge owing to their high accuracy and specificity. Herein, an AND logic gated-DNA nanodevice, based on the fluorescence nucleic acid probe and polymer-modified MnO nanosheets, for glutathione (GSH)-gated miRNA-21 signal amplification and GSH-activated magnetic resonance (MR) imaging-guided chemodynamic therapy (CDT) is reported. In the presence of overexpressed miRNA and GSH (tumor cells), the nanodevice can be in situ activated and release significantly amplified fluorescence signals and MR signals. Conversely, the fluorescence signal is quenched and MR signal remains at the background level with low miRNA and GSH (normal cells), efficiently reducing the false-positive signals by more than 50%. Under the guide of miRNA profiling and MR imaging, the tumor-responsive hydroxyl radical (·OH) can effectively kill tumor cells. Furthermore, the nanodevice shows catalase-like activity and glucose oxidase-like activity with the performance of O production and glucose consumption. This is the first time to fabricate a tumor-responsive theranostic DNA nanodevice with tumor-specific signal amplification of microRNA and GSH-activated MR imaging for CDT, potential hypoxia relief and starvation therapy, which provides a new insight for designing smart theranostic strategies.

摘要

开发具有高准确性和特异性的肿瘤诊治策略仍然是一个挑战。在此,我们报道了一种基于荧光核酸探针和聚合物修饰的 MnO 纳米片的与或逻辑门控 DNA 纳米器件,用于谷胱甘肽 (GSH) 门控 miRNA-21 信号放大和 GSH 激活磁共振 (MR) 成像引导的化学动力学治疗 (CDT)。在过表达 miRNA 和 GSH(肿瘤细胞)存在的情况下,纳米器件可以原位激活并释放出显著放大的荧光信号和 MR 信号。相反,在 miRNA 和 GSH 水平较低(正常细胞)时,荧光信号被猝灭,MR 信号保持在背景水平,可有效降低假阳性信号超过 50%。在 miRNA 谱分析和 MR 成像的指导下,肿瘤响应性的羟基自由基 (·OH) 可以有效杀死肿瘤细胞。此外,该纳米器件具有类过氧化氢酶和葡萄糖氧化酶活性,可实现 O2 的产生和葡萄糖的消耗。这是首次构建具有 miRNA 和 GSH 激活的 MR 成像的肿瘤特异性信号放大的肿瘤诊治 DNA 纳米器件用于 CDT,具有潜在的缓解缺氧和饥饿治疗作用,为设计智能诊治策略提供了新的思路。

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