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

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Abstract
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 1O2via 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.
Funding Information
  • Ministry of Science and Technology of the People's Republic of China (2019YFA0110600, 2019YFA0110601, 2021YFE0205000)
  • China Postdoctoral Science Foundation (2021M692303, 2021M702334)
  • Central University Basic Research Fund of China (2021SCU12013)
  • China Scholarship Council
  • National Natural Science Foundation of China (52161145402, 52173133, 81971622, 82001824, 82071938)
  • Chunhui Program of the Ministry of Education
  • Med-X Center for Materials, Sichuan University (MCM202102)
  • Post-Doctor Research Project, West China Hospital, Sichuan University (2020HXBH004, 2020HXBH126)
  • Medical Science and Technology Project of Sichuan Provincial Health Commission (21PJ011)
  • 1?3?5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC21047)
  • Science and Technology Project of Sichuan Province (2019YJ0710, 2021YFH0135, 2021YJ0054)
  • Chengdu science and technology project (2021-YF05-01297-SN)

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