A Photoacoustic Probe for the Imaging of Tumor Apoptosis by Caspase-Mediated Macrocyclization and Self-Assembly.

Photoacoustic (PA) imaging shows promise in the sensitive detection of caspase-3 activated in early tumor apoptosis in response to chemotherapy; smart PA probes are thus in high demand. Herein, we report the first smart PA probe (1-RGD) responsive to caspase-3, enabling real-time and high-resolution imaging of tumor apoptosis. 1-RGD is designed to leverage the synergetic effect of active delivery and caspase-3 activation. It is selectively recognized by active caspase-3 to trigger peptide substrate cleavage and biocompatible macrocyclization-mediated self-assembly, leading to an amplified PA imaging signal and prolonged retention in apoptotic tumor cells. Strong, high-resolution PA images are obtained in chemotherapy-induced apoptotic tumors in living mice after intravenous administration with 1-RGD, facilitating sensitive reporting of caspase-3 activity and distribution within tumor tissues.