Key Takeaways & Executive Findings
- •• • Sonozyme integrates Pt NPs with Y-COF, achieving dual enzyme-mimicking activities (CAT and POD) that convert H2O2 into O2 and ·OH, alleviating hypoxia and boosting ROS storm; in vivo tumor suppression was significant with no systemic toxicity. • • The donor-acceptor structural design of Y-COF optimizes band positions, enhancing intrinsic sonodynamic activity; Pt NPs further improve exciton separation and transfer, increasing ultrasound-triggered ROS generation. • • Sonozyme demonstrates catalase-like and peroxidase-like activities, enabling cascade oxygenation and ROS amplification, which are critical for overcoming TME hypoxia and enhancing SDT efficacy. • • In vivo experiments show effective tumor growth inhibition under ultrasound irradiation with no observable systemic toxicity, indicating potential for clinical translation.
Abstract
Sonodynamic therapy (SDT) faces critical limitations from inefficient sonosensitizers and the hypoxic tumor microenvironment, which curtail reactive oxygen species (ROS) generation. Here, we report a dual enzyme-mimicking sonosensitizer, termed sonozyme, engineered by integrating platinum nanoparticles (Pt NPs) with a tailored covalent organic framework (Y-COF). The spatially separated donor-acceptor architecture optimizes the band position of Y-COF, conferring intrinsic sonodynamic activity. Pt NPs further enhance ultrasound-triggered ROS generation by promoting exciton separation and transfer. Notably, sonozyme exhibits catalase (CAT) and peroxidase (POD) mimetic activities, converting endogenous H2O2 into O2 and ·OH, thereby alleviating hypoxia and augmenting oxidative stress. In vitro assays demonstrated significantly enhanced ROS production and cancer cell death under ultrasound irradiation. In vivo studies confirmed that sonozyme effectively suppresses tumor progression without observable systemic toxicity. This work presents a paradigm for designing high-performance multifunctional sonosensitizers, offering a promising strategy for cancer therapy.
1. Introduction
Sonodynamic therapy (SDT) has emerged as a non-invasive anticancer modality, yet its clinical translation is hampered by insufficient ROS production stemming from low-efficiency sonosensitizers and the complex tumor microenvironment (TME). Conventional organic sonosensitizers suffer from suboptimal physiological stability, while inorganic nanomaterials exhibit rapid electron-hole recombination, collectively diminishing ROS generation. Moreover, hypoxia within the TME further impedes oxygen-dependent SDT, limiting therapeutic outcomes.
Covalent organic frameworks (COFs) offer a transformative platform for SDT due to their high crystallinity, tunable porosity, and large surface area. Their π-conjugated skeletons facilitate electron delocalization and exciton transfer, mitigating electron-hole recombination. However, current COF-based sonosensitizers often rely on loading small-molecule sensitizers or synthesizing COFs from sensitizer monomers, which may not fully exploit the structural advantages. This work introduces a dual enzyme-mimicking COF sonosensitizer (sonozyme) that integrates Pt NPs with a tailored Y-COF, addressing both ROS generation efficiency and TME hypoxia through cascade oxygenation and ROS storm, thereby potentiating SDT.
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HOU Chunyuan, ZHANG Yu, ZHU Bin, HAN Nan, ZHAO Ziyao, WAN Jun, FENG Shujun, LUO Jun (2026). A dual enzyme-mimicking COF sonosensitizer potentiates cancer sonodynamic therapy via cascade oxygenation and ROS storm. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-025-3806-0
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Frequently Asked Questions
What is the specific mechanism by which Pt NPs enhance the sonodynamic activity of Y-COF?
Pt NPs improve the sono-generated exciton separation and transfer dynamics, reducing electron-hole recombination and thereby enhancing ultrasound-triggered ROS generation.
How does sonozyme address tumor hypoxia?
Sonozyme exhibits catalase (CAT) mimetic activity, converting endogenous H2O2 into O2, which alleviates hypoxia and supports oxygen-dependent SDT.
What are the dual enzyme-mimicking activities of sonozyme and their roles?
Sonozyme mimics both catalase (CAT) and peroxidase (POD). CAT converts H2O2 to O2, while POD converts H2O2 to ·OH, thereby augmenting oxidative stress and enhancing the ROS storm.
What in vivo evidence supports the therapeutic efficacy and safety of sonozyme?
In vivo experiments demonstrated that sonozyme effectively suppresses tumor progression under ultrasound irradiation, with no observable systemic toxicity, indicating good biocompatibility.
What is the significance of the donor-acceptor structural design in Y-COF?
The spatially separated donor-acceptor architecture optimizes the band position of Y-COF, which endows sonozyme with good intrinsic sonodynamic activity, facilitating efficient ROS generation.
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