Catalytic DNA circuits are desirable for sensitive bioimaging in living cells; yet, it remains a challenge to monitor these intricate signal communications because of the uncontrolled circuitry leakage and insufficient cell selectivity. Herein, a simple yet powerful DNA-repairing enzyme (APE1) activation strategy is introduced to achieve the site-specific exposure of a catalytic DNA circuit for realizing the selectively amplified imaging of intracellular microRNA and robust evaluation of the APE1-involved drug resistance. Specifically, the circuitry reactants are firmly blocked by the enzyme recognition/cleavage site to prevent undesirable off-site circuitry leakage. The caged DNA circuit has no target-sensing activity until its circuitry components are activated via the enzyme-mediated structural reconstitution and finally transduces the amplified fluorescence signal within the miRNA stimulation. The designed DNA circuit demonstrates an enhanced signal-to-background ratio of miRNA assay as compared with the conventional DNA circuit and enables the cancer-cell-selective imaging of miRNA. In addition, it shows robust sensing performance in visualizing the APE1-mediated chemoresistance in living cells, which is anticipated to achieve in-depth clinical diagnosis and chemotherapy research.

中文翻译：

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用于 miRNA 癌细胞选择性成像和耐药性稳健评估的多重保证催化 DNA 电路

催化 DNA 电路对于活细胞中的灵敏生物成像来说是理想的选择；然而，由于不受控制的电路泄漏和电池选择性不足，监测这些复杂的信号通信仍然是一个挑战。在此，引入了一种简单而强大的DNA修复酶（APE1）激活策略，以实现催化DNA电路的位点特异性暴露，从而实现细胞内microRNA的选择性放大成像和对APE1相关耐药性的稳健评估。具体而言，电路反应物被酶识别/裂解位点牢固地阻断，以防止不期望的场外电路泄漏。笼状 DNA 电路不具有目标传感活性，直到其电路组件通过酶介导的结构重建被激活，并最终在 miRNA 刺激下转导放大的荧光信号。与传统的 DNA 电路相比，设计的 DNA 电路显示出 miRNA 检测的信号背景比增强，并且能够实现 miRNA 的癌细胞选择性成像。此外，它在可视化活细胞中APE1介导的化疗耐药性方面表现出强大的传感性能，有望实现深入的临床诊断和化疗研究。