Enzymatically Activated Autonomous-Motion DNAzyme Signal Amplification Strategy for Tumor Cell-Specific Molecular Imaging with Improved Spatial Specificity

Strategies for achieving tumor-specific molecular imaging based on signal amplification hold great potential for evaluating the risk of tumor metastasis and progression. However, traditional amplification strategies are still constrained with limited tumor specificity because of the off-tumor signal leakage. Herein, an endogenous enzyme-activated autonomous-motion DNAzyme signal amplification strategy (E-DNAzyme) was rationally designed for tumor-specific molecular imaging with improved spatial specificity. The sensing function of E-DNAzyme can be specifically activated by the overexpressed apurinic/apyrimidinic endonuclease 1 (APE1) in the cytoplasm of tumor cells instead of normal cells, ensuring the tumor cell-specific molecular imaging with improved spatial specificity. Of note, benefiting from the target analogue-triggered autonomous motion of the DNAzyme signal amplification strategy, the detection limit can be decreased by approx. ∼7.8 times. Moreover, the discrimination ratio of tumor/normal cells of the proposed E-DNAzyme was ∼3.44-fold higher than the traditional amplification strategy, indicating the prospect of this universal design for tumor-specific molecular imaging.