An Activatable Near-Infrared Molecular Chemiluminescence Probe for Visualization of NQO1 Activity In Vivo

Chemiluminescence(CL)is a promising tool for diagnostics and sensing due to its inherent excitation light-free.However,most CL probes emit exclusively visible light with limited penetration depth,hindering their broad application for in vivo deep tissue imaging.This work reports an activated unimolecular CL probe(CL-P)that emits light in the near-infrared(NIR)region allowing a superior real-time visualization and detection of NAD(P)H quinone oxidoreductase 1(NQO1)in vivo.The NQO1-specific trimethyl-locked quinone is a lock for masking the NQO1 trigger site,and it was conjugated on the NIR Schaap's dioxetane chemiluminophore,achieving not only a subtle signal-to-noise ratio even at a depth of 15 mm in the chicken breast tissues,but also sensitively detecting the positive expression of NQO1 in A549 cells.CL-P has been successfully used for visualizing the aberrantly expressed NQO1 in subcutaneous xenograft A549 tumors.To our knowledge,this is the first work reporting the detection of NQO1 activity in the NIR region by unimolecular CL mode.Overall,the NQO1-activated visualization platform provides a guideline to transform a unimolecular CL sensor into a licensed imaging agent for the in vivo detection of enzyme-related diseases.