The School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, PR China; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, Fujian Province, 350108, PR China.
The School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, PR China; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, Fujian Province, 350108, PR China.
Biosens Bioelectron. 2021 Feb 1;173:112834. doi: 10.1016/j.bios.2020.112834. Epub 2020 Nov 20.
Exosomal microRNAs (miRNAs) are vital biomarkers for early diagnosis and prognosis monitoring of cancer. Yet, convenient and controllable detection of exosomal miRNA still remains challenges because of lacking of adequately simple and robust assay platforms. In this paper, it is first time to study the visible-light-induced oxidase mimic activity of 10-methyl-2-amino-acridone (MAA) being able to be switched by Cu and DNA. Based on this phenomenon, a series of visual molecular logic gates are constructed, and a colorimetric strategy has been developed to achieve exosomal microRNA-21 (miR-21) detection with a signal amplification approach. The visible-light-induced oxidase mimic activity of MAA can be inhibited by Cu. In presence of target, a large amount of capture probes partly complementary with miR-21 are hydrolyzed with the assist of duplex-strand specific nuclease (DSN), releasing guanine-rich oligodeoxynucleotides that can chelate Cu, resulting in catalytic activity of MAA being recovered under irradiation. This strategy allows the detection of miR-21 with a light modulating temporal controllable manner, and the linear range is from 50 fM to 3000 fM with the limit of detection (LOD) being 44.76 fM. More importantly, the proposed method can achieve quantitative measurement of exosomal miR-21 that is derived from three-dimensional multicellular tumor spheroids with different size, which is able to monitor the growth of tumor spheroids. This work is potential to provide a feasible tool for application in exosomal miRNAs-based cancer diagnosis. Ultimately, MAA is expected to be a signal probe in biomedical field by virtue of its fascinating visible-light-induced oxidase mimic activity.
外泌体 microRNAs (miRNAs) 是癌症早期诊断和预后监测的重要生物标志物。然而,由于缺乏足够简单和稳健的检测平台,外泌体 miRNA 的方便和可控检测仍然存在挑战。在本文中,首次研究了 10-甲基-2-氨基吖啶酮 (MAA) 的可见光诱导氧化酶模拟活性,该活性可被 Cu 和 DNA 开关调控。基于这一现象,构建了一系列可视化分子逻辑门,并开发了一种比色策略,通过信号放大方法实现了外泌体 microRNA-21 (miR-21) 的检测。MAA 的可见光诱导氧化酶模拟活性可被 Cu 抑制。在存在靶标的情况下,大量与 miR-21 部分互补的捕获探针在双链特异性核酸酶 (DSN) 的辅助下被水解,释放富含鸟嘌呤的寡脱氧核苷酸,这些核苷酸可以螯合 Cu,从而在光照下恢复 MAA 的催化活性。该策略允许以光调控的时间可控方式检测 miR-21,线性范围为 50 fM 至 3000 fM,检测限 (LOD) 为 44.76 fM。更重要的是,该方法能够定量测量源自不同大小三维多细胞肿瘤球体的外泌体 miR-21,从而能够监测肿瘤球体的生长。这项工作有望为基于外泌体 miRNAs 的癌症诊断提供一种可行的工具。最终,由于其引人注目的可见光诱导氧化酶模拟活性,MAA 有望成为生物医学领域的信号探针。