Artesunate-Based Multifunctional Nanoplatform for Photothermal/Photoinduced Thermodynamic Synergistic Anticancer Therapy

Thermodynamic therapy (TDT), one that uses heat to activate thermosensitizers and produce reactive oxygen species (ROS), has recently emerged as an attractive approach for cancer therapy. However, the development of safe and efficient thermosensitizers for TDT remains a big challenge. Here, we have found that artesunate (ARS) could produce ROS upon heating. Based on this interesting result, we have designed and prepared a pH-sensitive liposomal nanoplatform (ICG-ARS@NPs) composed of indocyanine green (ICG) and ARS for photoinduced TDT as well as photothermal therapy (PTT). Under the slightly acidic conditions in tumor tissues, the pH-sensitive liposomal ICG-ARS@NPs were able to release their drug cargos. Upon near-infrared irradiation, the photothermal agent ICG generated in situ hyperthermia and triggered the thermal sensitizing activity of ARS to produce ROS, resulting in damage to cancer cells and tumor tissues. The heat-induced ROS generation of ARS was also confirmed both in vitro and in vivo. In addition, because of their specific tumor targeting and synergistic photothermal and thermodynamic effects, ICG-ARS@NPs exhibited highly efficient anticancer therapeutic efficacy in H22 tumor-bearing mice. We believe that this work will promote the exploration of TDT for cancer therapy as well as the application of the old drug, artemisinin.