NETosis-Inspired Cell Surface-Constrained Framework Nucleic Acids Traps (FNATs) for Cascaded Extracellular Recognition and Cellular Behavior Modulation.

Upon pathogenic stimulation, activated neutrophils release nuclear DNA into the extracellular environment, forming web-like DNA structures known as neutrophil extracellular traps (NETs), which capture and kill bacteria, fungi, and cancer cells. This phenomenon is commonly referred to as NETosis. Inspired by this, we introduce a cell surface-constrained web-like framework nucleic acids traps (FNATs) with programmable extracellular recognition capability and cellular behavior modulation. This approach facilitates dynamic key chemical signaling molecule recognition such as adenosine triphosphate (ATP), which is elevated in the extracellular microenvironment, and triggers FNA self-assembly. This, in turn, leads to in situ tightly interwoven FNAs formation on the cell surface, thereby inhibiting target cell migration. Furthermore, it activates a photosensitizer-capturing switch, chlorin e6 (Ce6), and induces cell self-destruction. This cascade platform provides new potential tools for visualizing dynamic extracellular activities and manipulating cellular behaviors using programmable in situ self-assembling DNA molecular devices.

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.