Poly(Amino Acid) Coordination Nanoparticle as a Potent Sonosensitizer for Cancer Therapy

Sonodynamic therapy (SDT) has gained widespread attention owning to its much deeper tissue penetration depth compared with phototherapy. However, developing sonosensitizers with high sonosensitization efficacy in a tumor hypoxic environment is still a significant challenge. Herein, we fabricated a poly(amino acid) coordination nanoparticle (PFHF) as a potent sonosensitizer with great biocompatibility and high hydroxyl radical (•OH)-generation capacity for efficient SDT. PFHF was identified as a hexa-coordination structure by X-ray absorption fine structure and density functional theory. Furthermore, PFHF could be excited by ultrasound, which directly cleaved H2O into •OH, achieving oxygen-independent SDT. In addition, doxorubicin-loaded PFHF achieved a significant synergistic chemo-sonodynamic therapeutic effect with a tumor inhibition rate of 89%. The poly(amino acid) coordination nanoparticle with good biocompatibility and oxygen-independent ability could provide an idea for the rational design of sonosensitizers.