Activatable Ferritin Nanocomplex for Real-Time Monitoring of Caspase-3 Activation during Photodynamic Therapy

One mechanism of photodynamic therapy (PDT) for the ablation of tumors is to induce apoptosis. Visualization of apoptosis during PDT in real-time is of great benefit for predicting and evaluating therapeutic outcomes. Herein, we engineered a highly stable and sensitive caspase-3 ferritin activatable probe (FABP/ZnPc) for simultaneous delivery of a photosensitizer (ZnPc) and real-time visualization of apoptosis during PDT. Upon near-infrared (NIR) light irradiation, ZnPc becomes active and initiates apoptosis, upon which the outer layer of the FABP/ZnPc is degraded by the apoptotic marker, caspase-3, to boost strong fluorescent signals, ultimately allowing real-time imaging of apoptosis. Our results demonstrate the utility of FABP/ZnPc as a tool for PDT and simultaneous imaging of caspase-3 activation in vitro and in vivo. Overall, the ability of FABP/ZnPc to image apoptosis during PDT will not only facilitate optimizing and personalizing the PDT strategy but is also important for understanding the mechanisms of PDT.