Molecular Visualization of Early-Stage Acute Kidney Injury with a DNA Framework Nanodevice.
Molecular Visualization of Early-Stage Acute Kidney Injury with a DNA Framework Nanodevice.
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早期急性肾损伤的DNA框架纳米装置的分子可视化。
DOI：
10.1002/advs.202105947
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发表时间：
2022-07
期刊：
影响因子：
15.1
通讯作者：
Xia, Qiang
中科院分区：
文献类型：
--
作者：
Ding, Fei;Zhang, Shuangye;Liu, Suyu;Feng, Jing;Li, Jiang;Li, Qian;Ge, Zhilei;Zuo, Xiaolei;Fan, Chunhai;Xia, Qiang
关键词：
具有人工智能的DNA纳米机器引起了人们的极大兴趣，这可能会开启精准医疗的新时代。然而，它们的体内行为，包括早期诊断和治疗效果受到其靶向效率的限制。在这里，开发了一种基于四面体DNA框架（TDF）的纳米装置，用于早期阿基的体内近红外（NIR）诊断。该纳米器件包括三个功能模块：作为肾脏靶向载体的尺寸可调的TDF纳米结构，生物标志物肾损伤分子-1（Kim-1）的结合模块和NIR信号模块。这些模块的合作允许纳米器件选择性地在具有高Kim‐1水平的受损肾脏组织中积累，产生强的NIR荧光;而具有适当尺寸的纳米器件可以在健康肾脏中快速清除，以最大限度地减少背景。通过使用这种纳米器件，阿基发作的早期诊断至少比Kim‐1尿液分析提前6小时或比血液检测提前12小时。据设想，这种基于TDF的纳米器件可能对阿基和其他肾脏疾病的早期诊断有意义。基于四面体DNA框架的纳米器件集成了三种功能，允许以高对比度的方式真实的实时跟踪肾损伤分子-1的动态变化，并且可以用作成像剂和尿液分析示踪剂，以非侵入性地诊断急性肾损伤的发作，其可以比常规体外测定更早地检测到。
DNA nanomachines with artificial intelligence have attracted great interest, which may open a new era of precision medicine. However, their in vivo behavior, including early diagnosis and therapeutic effect are limited by their targeting efficiency. Here, a tetrahedral DNA framework (TDF)‐based nanodevice for in vivo near‐infrared (NIR) diagnosis of early‐stage AKI is developed. This nanodevice comprises three functional modules: a size‐tunable TDF nanostructure as kidney‐targeting vehicle, a binding module for the biomarker kidney injury molecule‐1 (Kim‐1), and a NIR signaling module. The cooperation of these modules allows the nanodevice to be selectively accumulated in injured kidney tissues with high Kim‐1 level, generating strong NIR fluorescence; whereas the nanodevice with the proper size can be rapidly cleared in healthy kidneys to minimize the background. By using this nanodevice, the early diagnosis of AKI onset is demonstrated at least 6 h ahead of Kim‐1 urinalysis, or 12 h ahead of blood detection. It is envisioned that this TDF‐based nanodevice may have implications for the early diagnosis of AKI and other kidney diseases. A tetrahedral DNA framework‐based nanodevice integrating three functionalities allows real‐time tracking of the dynamic variation of kidney injury molecule‐1 in high contrast manner, and can be used as imaging agent and urinalysis tracers to non‐invasively diagnose the onset of acute kidney injury earlier than that can be detected by the conventional in vitro assays.
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