Engineering Molecular Probes for In Vivo Near-Infrared Fluorescence/Photoacoustic Duplex Imaging of Human Neutrophil Elastase

Early detection of human neutrophil elastase (HNE), the potential biomarker of lung cancer, is crucial for the accurate diagnosis and evaluation of lung cancer. Currently, little progress of HNE-activated probes has been made for in vivo imaging. Herein, assisted by probe-active pocket match engineering, we synthesized a series of near-infrared fluorescence (NIRF) and photoacoustic (PA) duplex imaging probes by conjugating diverse fluorinated amide chains onto hemi-cyanine. Finally, we identified that probe 2 (denoted as LET-8), with the pentafluoroethyl group, is a superior probe to detect HNE with the best selectivity as well as good response ability and thus successfully realized NIRF/PA duplex imaging of HNE activity both in vitro and in vivo.