Journal Article

A Hypoxia‐Responsive Single‐Atom Sonozyme for Targeted Sonocatalytic Therapy in Alleviating Atherosclerotic Plaque

Huang, Canxia, Zheng, Minglong, Zhu, Shuang, Wang, Jingfeng, Zhang, Yuling, Li, Ruonan, He, Li, Huang, Tongsheng, Pan, Yue, Liu, Zhiwen, Yuan, Guotao, Cao, Zhengyu, Chen, Qiaofei, Zhang, Pingyu, Wen, Kexin

2025

Overview

Sonocatalytic therapy (SCT) offers a non‐invasive and deep tissue‐penetrating approach to addressing the pathological challenges of atherosclerosis. However, its therapeutic efficacy remains limited by the lack of efficient sonosensitizers. A critical challenge in SCT is simultaneously leveraging beneficial plaque microenvironment factors, such as elevated H2O2 levels, while mitigating adverse conditions, including hypoxia. Herein, a microenvironment‐regulatable single‐atom sonozyme system is presented to enable effective SCT while simultaneously refining the lesion microenvironment. The single‐atom manganese catalyst (SMC) is synthesized via MOF‐derived precursor pyrolysis followed by ion implantation, yielding atomically precise four‐coordinated active sites. Functionalized with hyaluronic acid (HA) facilitates targeted delivery of SMC‐HA to M1 macrophages. Under ultrasound (US), SMC‐HA effectively eliminates M1 macrophages, thereby reducing plaque burden and promoting lesion regression in two ApoE−/− mice models. Overall, SMC‐HA reinforces its role as an advanced sonosensitizer for SCT. This study establishes SMC‐HA‐mediated SCT as a promising therapeutic strategy for atherosclerotic plaque treatment. A tetranitrogen‐coordinated single‐atom manganese catalyst (SMC) is fabricated with outstanding sonosensitization efficiency and multi‐enzyme‐like catalytic properties. To enable better targeting of M1 macrophages, hyaluronic acid (HA) is applied to modify the surface of SMC, yielding SMC‐HA nanozymes. The SMC‐HA exhibits superior sonocatalytic activity. Finally, the as‐synthesized SMC‐HA demonstrates significantly enhanced anti‐atherosclerotic effect in ApoE–/– mouse model.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Animals / Apoptosis / Atherosclerosis / Atherosclerosis - therapy / Carbon / Catalysis / Disease Models, Animal / Efficiency / Enzymes / Fourier transforms / Hyaluronic Acid / Hypoxia / Hypoxia - metabolism / Macrophages - metabolism / Manganese / Medical diagnosis / Mice / Mice, Inbred C57BL / Nanomaterials / Nanotechnology / Oxidation / plaque microenvironment / Plaque, Atherosclerotic - metabolism / Plaque, Atherosclerotic - therapy / single‐atom catalyst / single‐atom nanozymes / sonocatalytic therapy / Spectrum analysis / Transmission electron microscopy / Ultrasonic Therapy - methods