Enzymatically triggered DNA nanodevices for dynamic monitoring of epithelial-mesenchymal transition via duplexed miRNA imaging

Despite microRNAs (miRNAs) are key regulators of epithelial-mesenchymal transition (EMT), approaches allowing for real-time monitoring of EMT process of tumor cells via miRNA imaging have yet to be achieved. Herein we present the design of an enzyme-controlled DNA nanodevice for activatable parallel imaging of two independent target miRNAs, thus achieving cancer cell-specific monitoring of EMT process. Toehold -mediated strand displacement reactions and enzyme activatable modules are integrated in the DNA na-nodevice design to achieve generation of multiple signal outputs in response to different miRNA inputs. The system allows for enzymatically activatable two-input and three-output imaging patterns in cancer cells, while possesses no miRNA sensing functions in normal cells, resulting in an enhanced sensitivity and cell specificity for the cancer-selective monitoring of EMT dynamics. Furthermore, it is demonstrated that the DNA nanodevice can rapidly discriminate EMT state of chemoresistant carcinoma cells by duplexed miRNA imaging in an enzyme-activated manner. We envision the application of this multiplexed imaging tech-nology for decoding the roles of EMT in diverse pathological processes.(c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

In this study, an enzyme-controlled DNA nanodevice was designed for the real-time monitoring of miRNA imaging during the epithelial-mesenchymal transition (EMT) process of tumor cells, achieving cancer cell-specific monitoring of EMT process. The integration of toehold-mediated strand displacement reactions and enzyme activatable modules allows for the generation of multiple signal outputs in response to different miRNA inputs. The system enables enzymatically activatable two-input and three-output imaging patterns in cancer cells, while lacking miRNA sensing functions in normal cells, resulting in enhanced sensitivity and cell specificity for the cancer-selective monitoring of EMT dynamics.