Poly(Amino Acid) Coordination Nanosonosensitizer as a ROS Amplifier for Enhanced Sonodynamic-Chemodynamic Therapy

Sonodynamic therapy (SDT) has gained widespread attention owing to its low invasiveness and target specificity. However, developing high biocompatibility sonosensitizers with high sonosensitization efficacy in a tumor hypoxic and reductive microenvironment is still a significant challenge. Herein, we fabricated a poly(amino acid) coordination nanoparticle (PFHCu) as a potent sonosensitizer and dual nanoenzyme with great biocompatibility and high reactive oxygen species (ROS) generation capacity for efficient SDT and chemodynamic therapy (CDT). PFHCu owns dual nanoenzyme properties of CAT and POD-like activities, catalyzing H₂O₂ to generate O₂ and •OH, enhancing sonodynamic efficiency to induce a large amount of ¹O₂. Moreover, PFHCu as a ROS amplifier can deplete glutathione to accumulate intracellular oxidative stress, leading to self-cyclically amplify dual-ROS enhancement for synergistic SDT-CDT. In addition, doxorubicin-loaded PFHCu achieves a significant synergistic SDT, CDT, and chemotherapy with a substantial cell-killing rate of 77%. The poly(amino acid) coordination nanosonosensitizer with good biocompatibility and ROS amplifier ability could provide an idea for the theoretical design of sonosensitizers.