GSH‐Depleted PtCu3 Nanocages for Chemodynamic‐ Enhanced Sonodynamic Cancer Therapy

Abstract The ultrahigh concentration of glutathione (GSH) inside tumors destroys reactive oxygen species (ROS)‐based therapy, improving the outcome of chemodynamic therapy (CDT)‐enhanced sonodynamic therapy (SDT) by depleting GSH is full of great challenge. Herein, PtCu 3 nanocages are first reported as acting as a sonosensitizer with highly efficient ROS generation under ultrasound irradiation. In addition, PtCu 3 nanocages can act as horseradish peroxidase‐like nanozymes, catalyzing the decomposition of H 2 O 2 into • OH under acidic conditions for CDT. Surprisingly, PtCu 3 nanocages can act as another kind of nanozyme, mimicking glutathione peroxidase (GSH‐Px), which plays an important role in accelerating GSH depletion by oxidizing molecules, further weakening the capacity of tumor cells scavenging ROS by GSH. Both in vitro and in vivo studies demonstrate that PtCu 3 nanocages perform well in reducing GSH level for CDT‐enhanced SDT. Moreover, utilizing the high absorption in the near‐infrared region and strong X‐ray attenuation ability, the PtCu 3 nanocages are able to conduct photoacoustic/computed tomography dual‐modal imaging‐guided combined cancer therapy. It is worth mentioning that PtCu 3 nanocages cause minimal toxicity to normal tissues at therapeutic doses. This work highlights the use of PtCu 3 nanocages for effective CDT‐enhanced SDT via GSH depletion.