Abstract
PURPOSE: This study aimed to develop a composite nanozyme system (Au/PB-Ce6-HA) based on gold nanoparticles (AuNPs) and Prussian blue nanoparticles (PBNPs) to combat tumor hypoxia and insufficient endogenous hydrogen peroxide (H(2)O(2)) deficiency, thus enhancing the efficacy of sonodynamic therapy (SDT) and starvation therapy for liver cancer. METHODS: The Au/PB-Ce6-HA system was constructed by in situ embedding AuNPs on PBNPs, loading the sonosensitizer Chlorin e6 (Ce6), and surface-coating with thiolated hyaluronic acid (HA-SH). The system was evaluated both in vitro and in vivo to assess its ability to catalyze glucose to generate H(2)O(2), decompose H(2)O(2) to produce oxygen, and generate highly toxic reactive oxygen species (ROS) under ultrasound irradiation. RESULTS: The Au/PB-Ce6-HA nanozymes demonstrated high catalytic activity, thus significantly improving SDT and starvation therapy. Specifically, the system effectively deprived tumors of their energy supply by generating H(2)O(2), while simultaneously producing oxygen to enhance cytotoxic ROS generation under ultrasound irradiation. Both in vivo and in vitro studies further demonstrated a synergistic effect in inhibiting tumor growth while enhancing therapeutic efficacy. CONCLUSION: An intelligent composite nanomaterial was successfully developed, combining starvation therapy and sonodynamic therapy to significantly enhance the treatment of liver cancer. The Au/PB-Ce6-HA nanozyme system demonstrated excellent synergy in both in vitro and in vivo settings, offering a promising strategy for cancer therapy.