A membrane-protein targeted DNA multitasking processor for precise tumor cell imaging

Abstract

DNA nanodevices based on nucleic acid aptamers have become powerful tools for tumor imaging. However, the problem of “on-target, off-tumor” has always been a challenge for intelligent molecular probes to identify tumors. In order to achieve precise identification and tumor microenvironment (TEM) localization of cancer cells, we integrated membrane protein aptamers with two reporter molecules, imotif (pH reporter) and ATP aptamer (ATP reporter), which can respond to specific biomarkers in TME, and developed a Y-shaped multitasking processor (Y-smp). This Y-shaped multitasking processor can target membrane protein overexpressed on the surface of cancer cells, allowing them to remain on the cell surface. At the same time, the two reporter probes work independently in response to acidity and ATP, undergo conformational changes and detach from Y-smp, carrying away quenching groups to produce green fluorescence signals corresponding to ATP molecules and red fluorescence signals corresponding to acidity. The Y-shaped multitasking processor can generate different fluorescent signals corresponding to two microenvironment markers, and does not interfere with each other in a simulated tumor microenvironment characterized by weak acidity and abundant ATP. The simple and intuitive molecular probe recognition strategy provides the possibility for precise localization and recognition of cancer cells.