Mucin 1 (MUC1) is abnormally expressed in tumor tissues, and quantitative analysis of MUC1 is thus beneficial to the prevention and early diagnosis of cancer. In this work, by intergrating DNAzyme with strand displacement reaction (SDR), we have fabricated a highly sensitive MUC1 colorimetric assay based on a multiple signal amplification strategy. Specifically, the presence of MUC1 can induce the exposure of the toehold region pre-locked in the aptamer probe (AP) to initiate SDR, liberating the MUC1/AP complex for recycling (cycle I) and forming the dimer-like DNAzyme. The formed DNAzyme can then cyclically cleave the substrate signal probe (cycle II), triggering the formation of G-quadruplex sequence and the new active enzyme sequence that can also cleave the signal probe (cycle III). Such target-induced triple amplification reaction can generate massive G-quadruplex sequences, which leads to a dramatically enhanced colorimetric signal for sensitive detection of MUC1 even at an ultra-low level of 35 pM. The colorimetric strategy also holds a high selectivity to distinguish MUC1 from other interfering proteins and can be successfully applied to the detection of MUC1 in human serum as well as cancer cells, presenting great potential in biosensing and clinical diagnostics.

粘蛋白1（MUC1）在肿瘤组织中异常表达，因此MUC1的定量分析有利于癌症的预防和早期诊断。在这项工作中，通过将DNAzyme与链置换反应（SDR）整合在一起，我们基于多信号放大策略制备了高度灵敏的MUC1比色测定法。具体而言，MUC1的存在可以诱导预先锁定在适体探针（AP）中的脚尖区域的暴露，从而引发SDR，释放MUC1 / AP复合物以进行再循环（循环I）并形成二聚体样DNAzyme。然后，形成的DNA酶可以循环切割底物信号探针（循环II），触发G-四链体序列的形成和新的活性酶序列也可以切割信号探针（循环III）。这种靶标诱导的三重扩增反应可以生成大量的G-四链体序列，即使在35 pM的超低水平下，也能显着增强比色信号，以灵敏地检测MUC1。比色法还具有很高的选择性，可将MUC1与其他干扰蛋白区分开，可成功应用于人血清和癌细胞中MUC1的检测，在生物传感和临床诊断中具有巨大潜力。