Multiple signal amplification via coupling DNAzyme with strand displacement reaction for sensitive colorimetric analysis of MUC1

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.