Enzyme Translocation‐Mediated Signal Amplification for Spatially Selective Aptasensing of ATP in Inflammatory Cells

Abstract Amplified ATP imaging in inflammatory cells is highly desirable. However, the spatial selectivity of current amplification methods is limited, that is, signal amplification is performed systemically and not in a disease site‐specific manner. Here we present a versatile strategy, termed enzymatically triggerable, aptamer‐based signal amplification (ETA‐SA), that enables inflammatory cell‐specific imaging of ATP through spatially‐resolved signal amplification. The ETA‐SA leverages a translocated enzyme in inflammatory cells to activate DNA aptamer probes and further drive cascade reactions through the consumption of hairpin fuels, which, however, exerts no ATP response activity in normal cells, leading to a significantly improved sensitivity and spatial specificity for the inflammation‐specific ATP imaging in vivo. Benefiting from the improved spatial selectivity, enhanced signal‐to‐background ratios were achieved for ATP imaging during acute hepatitis.