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 center dot OH via a cascade chemodynamic path and also (1)O(2)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.

Automated summary

The development of novel spiky cascade biocatalysts for US-enhanced tumor therapy shows promise in generating reactive oxygen species (ROS) and improving treatment efficacy, particularly in inducing apoptosis in malignant melanoma cells. These efficient peroxisome-mimetic cascade-catalytic strategies hold potential for clinical tumor therapies.