Abstract：
Stimulus-responsive mode is highly desirable for improving the precise monitoring and physiological efficacy of endogenous biomarkers (EB). However, its integrated application for visual detection and therapy is limited by inappropriate use of responsive triggers and poor delivery of EB signal-transducing agents, which remain challenging in simultaneous monitoring and noninvasive therapy of EB and EB-mediated pathological events. Target microRNA (miRNA) as controllable reaction triggers and DNAzyme as signal-transducing agent are proposed to develop target-stimulated multifunctional nanocabinets (MFNCs) for the visual tracking of both miRNA and miRNA-mediated anticancer events. The MFNCs, equipped with a target-discriminating sequence-incorporated DNAzyme motif, can specifically release therapeutic molecules through target-triggered conformational switches, accompanied by transduction signal output. Target detection and molecule release performance are recorded in parallel via reverse dual-signal feedback at the single-molecule level. In addition, the intrinsic thermal-replenishing of the MFNCs leads to tumor ablation without invasive exogenous aids. The system achieves visual target quantification, anticancer molecule real-time tracking, and tumor suppression in vivo and in vitro. This work proposes a new paradigm for precise visual exploration of EB or EB-mediated bio-events and provides a demonstration of efficacious all-in-one detection and therapy based on the target-triggered multifunctional nanosystem.
摘要：
刺激响应模式对于改善内源性生物标志物(EB)的精确监测和生理功效是高度期望的。然而,其在视觉检测和治疗方面的综合应用受到反应性触发器的不当使用和EB信号传导剂传递不良的限制，在同时监测和无创治疗EB和EB介导的病理事件方面仍然具有挑战性。作为可控反应触发因子的靶微小RNA（miRNA）和作为信号转导剂的DNAzyme被提议用于开发用于视觉跟踪miRNA和miRNA介导的抗癌事件的靶刺激的多功能纳米载体（MFNC）。MFNC,配备有靶识别序列结合的DNA酶基序，可以通过靶标触发的构象开关特异性释放治疗分子，伴随着转导信号输出。通过在单分子水平的反向双信号反馈并行记录靶标检测和分子释放性能。此外,MFNC的内在热补充导致肿瘤消融，而没有侵入性外源性辅助。该系统实现了可视化目标的量化,抗癌分子实时跟踪，和体内外肿瘤抑制。这项工作提出了一种精确视觉探索EB或EB介导的生物事件的新范例，并提供了基于靶标触发的多功能纳米系统的有效一体化检测和治疗的演示。
