A Biocompatible Probe for the Detection of Neutrophil Elastase Free from the Interference of Structural Changes and Its Application to Ratiometric Photoacoustic Imaging In Vivo

Abstract Neutrophil elastase (NE) plays a key role in chronic inflammation and acute responses to infection and injury. Effective disease interventions thus call for precise identification of NE to aid the clinical treatment of such diseases. However, the detection process suffers from the interference of structural changes of NE. Herein, we introduce a molecular probe with high biocompatibility to overcome the interference, which was achieved by combining theoretical calculations and experimental studies, that permits highly specific and sensitive detection of NE in cells and in vivo. The upregulated NE accumulation was specifically measured in inflammation by ratiometric photoacoustic and near‐infrared fluorescence imaging, providing a new method for developing more specific fluorogenic probes for other enzymes.