A Caspase-3-Activatable Near-Infrared AIEgen for Tumor Apoptosis Imaging In Vivo

Near-infrared (NIR) fluorescence imaging of tumor caspase-3 activity can be applied for real-time monitoring of the therapeutic effect of an anticancer drug in vivo. Aggregation-induced emission luminogens (AIEgens) are highly sensitive, unique fluorophores, but there is no NIR AIEgen reported for the above purpose. Herein, we rationally developed an activatable NIR AIEgen, Ac-Asp-Glu-Val-Asp-Pra-QMT (Ac-DEVD-Pra-QMT), to sensitively image caspase-3 activity in apoptotic 4T1 cells and tumor. After being internalized by cisplatin-induced apoptotic tumor cells, Ac-DEVD-Pra-QMT is subjected to caspase-3 cleavage to yield hydrophobic Pra-QMT, which spontaneously aggregates into nanoparticles to turn "On" the NIR fluorescence. Experimental results show that Ac-DEVD-Pra-QMT renders 14.9-fold and 2.7-fold higher NIR fluorescent intensities compared to those of the control groups in vitro and in vivo, respectively. We expect that Ac-DEVD-Pra-QMT could serve as a valuable tool for the early tracking of chemotherapeutic effects in the near future.