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<p>Developing efficient and multifunctional sonosensitizers is critical for enhancing the efficacy of sonodynamic therapy (SDT). Herein, a dual enzyme-mimicking sonosensitizer, termed sonozyme, is prepared for improving the management of malignancy in SDT via cascade oxygenation and reactive oxygen species (ROS) storm, which consists of a tailored covalent organic framework (Y-COF) integrated with platinum nanoparticles (Pt NPs). Spatially separated donor-acceptor structural design optimizes the band position of Y-COF, which endows sonozyme with good intrinsic sonodynamic activity. Notably, Pt NPs improve the sono-generated exciton separation and transfer dynamics, further enhancing the ultrasound-triggered ROS generation ability of sonozyme. Particularly, sonozyme exhibits dual enzymatic activities, resembling both catalase (CAT) and peroxidase (POD), which enable the conversion of endogenous H<sub>2</sub>O<sub>2</sub> into O<sub>2</sub> and ·OH, thereby alleviating hypoxia while augmenting oxidative stress to enhance the SDT effect, ultimately resulting in significant tumor cell death. Further <i>in vivo</i> experiments demonstrate that sonozyme effectively suppresses tumor progression with concomitant absence of observable systemic toxicity under ultrasound irradiation. Therefore, sonozyme provides a paradigm for pioneering high-performance multifunctional sonosensitizers and presents a promising strategy for cancer therapy.</p>

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A dual enzyme-mimicking COF sonosensitizer potentiates cancer sonodynamic therapy via cascade oxygenation and ROS storm

  • 期刊论文

  • 发表日期：

    2026年2月4日

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  • Chunyuan Hou,
  • Yu Zhang,
  • Bin Zhu,
  • Nan Han,
  • Ziyao Zhao,
  • Jun Wan,
  • Shujun Feng,
  • Jun Luo

摘要

Developing efficient and multifunctional sonosensitizers is critical for enhancing the efficacy of sonodynamic therapy (SDT). Herein, a dual enzyme-mimicking sonosensitizer, termed sonozyme, is prepared for improving the management of malignancy in SDT via cascade oxygenation and reactive oxygen species (ROS) storm, which consists of a tailored covalent organic framework (Y-COF) integrated with platinum nanoparticles (Pt NPs). Spatially separated donor-acceptor structural design optimizes the band position of Y-COF, which endows sonozyme with good intrinsic sonodynamic activity. Notably, Pt NPs improve the sono-generated exciton separation and transfer dynamics, further enhancing the ultrasound-triggered ROS generation ability of sonozyme. Particularly, sonozyme exhibits dual enzymatic activities, resembling both catalase (CAT) and peroxidase (POD), which enable the conversion of endogenous H2O2 into O2 and ·OH, thereby alleviating hypoxia while augmenting oxidative stress to enhance the SDT effect, ultimately resulting in significant tumor cell death. Further in vivo experiments demonstrate that sonozyme effectively suppresses tumor progression with concomitant absence of observable systemic toxicity under ultrasound irradiation. Therefore, sonozyme provides a paradigm for pioneering high-performance multifunctional sonosensitizers and presents a promising strategy for cancer therapy.