Membrane Protein Guided and ATP-Gated Dual Module DNA Nanodevice for Amplified Fluorescence Labeling of Cancer Cells

The occurrence and progression of tumors are accompanied by changes in both the microenvironment and cancer cells. Therefore, the detection of extracellular alert molecule accumulation, as well as the identification of abnormal cancer biomarkers both contribute to the accurate localization of individual cancer cells. Here, we have designed a cancer cell fluorescence labeling nanodevice with a membrane protein targeting domain and extracellular ATP-fueled amplification switch. The AND logic-based nanodevice light-up the cancer cell membrane only in the coexistence of target membrane proteins and abnormal ATP concentration. We demonstrated the ability of the nanodevice to selectively label target cells in a cell mixture supplemented with ATP at concentrations within the range in the tumor microenvironment (1-5×10-4 M). Additionally, the modular design of DNA nanodevices enables broad application to different cancer cells by replacing them with corresponding membrane protein aptamers. Our fluorescence labeling nanodevice with signal amplification shows promise in serving as an imaging tool for visualizing the impact of ATP regulation on cancer evolution.