Cell-Membrane-Anchored DNA Logic-Gated Nanoassemblies for In Situ Extracellular Bioimaging

Extracellular K⁺ and adenosine triphosphate (ATP) levels are significantly elevated in the tumor microenvironment (TME) and can be used as biomarkers for early cancer detection and tumor localization. Most reported TME sensors only respond to single abnormal factors, resulting in a lack of accuracy and specificity for the detection of complex environments. Thus, precisely locating the TME remains challenging. In this work, we aimed to develop an intelligent DNA nanoassembly controlled by a "YES-AND" logic circuit using a bimolecular G-quadruplex (G4) and ATP aptamer as logical control units. As a proof of concept, in the presence of K⁺ (input 1) and ATP (input 2), the YES-AND Boolean operator returned a true value and the output was the fluorescence resonance energy transfer (FRET) signal, indicating high sensitivity and selectivity. After being anchored to living cell surfaces, this logic nanosensor imaged extracellular K⁺ and ATP present at abnormal levels in situ. Owing to diverse disease markers in the TME, this novel logic sensor might hold great promise for the targeted delivery of intelligent anticancer drugs and Boolean logic-controlled treatment.