Institute of Molecular Medicine, Department of Liver Surgery, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
Adv Sci (Weinh). 2022 Jul;9(20):e2105947. doi: 10.1002/advs.202105947. Epub 2022 May 4.
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.
具有人工智能的 DNA 纳米机器引起了极大的兴趣，这可能开启精准医疗的新时代。然而，它们在体内的行为，包括早期诊断和治疗效果，受到靶向效率的限制。在这里，开发了一种基于四面体形 DNA 框架（TDF）的纳米器件，用于体内近红外（NIR）诊断早期 AKI。该纳米器件包含三个功能模块：作为肾脏靶向载体的尺寸可调 TDF 纳米结构、用于生物标志物肾损伤分子-1（Kim-1）的结合模块，以及 NIR 信号模块。这些模块的协同作用使纳米器件能够选择性地在 Kim-1 水平较高的受损肾脏组织中积累，产生强烈的 NIR 荧光；而具有适当尺寸的纳米器件可以在健康的肾脏中迅速清除，以最小化背景。通过使用这种纳米器件，可以在 Kim-1 尿分析之前至少提前 6 小时，或在血液检测之前提前 12 小时，对 AKI 的早期发作进行诊断。可以预见，这种基于 TDF 的纳米器件可能对 AKI 和其他肾脏疾病的早期诊断具有重要意义。
