Spiky Cascade Biocatalysts as Peroxisome-Mimics for Ultrasound-Augmented Tumor Ablation

Ultrasound (US)-augmented tumor ablation with sono-catalysts has emerged as a promising therapeutic modality due to high tissue penetration, nonionizing performance, and low cost of US-based therapies. Developing peroxisome-mimetic cascade biocatalysts for US-augmented synergistic treatment would further effectively reduce the dependence of the microenvironment H₂O₂ and enhance the tumor-localized reactive oxygen species (ROS) generation. Here, we proposed and synthesized a novel spiky cascade biocatalyst as peroxisome-mimics that consist of multiple enzyme-mimics, i.e., glucose oxidase-mimics (Au nanoparticles for producing H₂O₂) and heme-mimetic atomic catalytic centers (Fe-porphyrin for ROS generation), for US-augmented cascade-catalytic tumor therapy. The synthesized spiky cascade biocatalysts exhibit an obvious spiky structure, uniform nanoscale size, independent of endogenous H₂O₂, and efficient US-responsive biocatalytic activities. The enzyme-mimetic biocatalytic experiments show that the spiky cascade biocatalysts can generate abundant ·OH via a cascade chemodynamic path and also ¹O₂ via US excitation. Then, we demonstrate that the spiky cascade biocatalysts show highly efficient ROS production to promote melanoma cell apoptosis under US irradiation without extra H₂O₂. Our in vivo animal data further reveal that the proposed US-assisted chemodynamic cascade therapies can significantly augment the therapy efficacy of malignant melanoma. We suggest that these efficient peroxisome-mimetic cascade-catalytic strategies will be promising for clinical tumor therapies.