Activatable Nanoprobe with Aggregation-Induced Dual Fluorescence and Photoacoustic Signal Enhancement for Tumor Precision Imaging and Radiotherapy

Owing to the high sensitivity and high spatial resolution, fluorescence (FL) imaging has been widely applied for visualizing biological processes. To gain insight into molecular events on deeper tissues, photoacoustic (PA) imaging with better deep-tissue imaging capability can be incorporated to provide complementary visualization and quantitative information on the pathological status. However, the development of activatable imaging probes to achieve both FL and PAsignal amplification remains challenging because the enhancement oflight absorption in PA imaging often caused the quenching of FL signal.Herein, wefirst developed a caspase-3 enzyme activatable nanoprobe ofa nanogapped gold nanoparticle coated with AIE molecule INT20 andDEVD peptides (AuNNP@DEVD-INT20) for tumor FL and PAimaging and subsequent imaging-guided radiotherapy. The nanoprobecould interact with GSH and caspase-3 enzyme to liberate INT20 molecules, leading to AIE. Simultaneously, thein situself-assembly of AuNPs was achieved through the cross-linking reaction between the sulfhydryl and the maleimide, resulting in ratiometric PAimaging in tumor. Remarkably, the nanoprobe can generate richful ROS for cancer radiotherapy under X-ray irradiation. The platform not only achieves the aggregation-induced FL and PA signal enhancement but also provides a general strategy for imaging of various biomarkers, eventually benefiting precise cancer therapy.