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具有多种酶活性的双金属氧化物Cu-FeO纳米簇用于伤口感染治疗和伤口愈合。

Bimetallic oxide Cu-FeO nanoclusters with multiple enzymatic activities for wound infection treatment and wound healing.

作者信息

Jin Xu, Shan Jie, Zhao Jiemin, Wang Tao, Zhang Wei, Yang Shijie, Qian Haisheng, Cheng Liang, Chen Xu-Lin, Wang Xianwen

机构信息

Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, P. R. China.

Institute of Clinical Pharmacology, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Anhui Medical University, Hefei 230022, P. R. China.

出版信息

Acta Biomater. 2023 Oct 28. doi: 10.1016/j.actbio.2023.10.028.

Abstract

Infections and oxidative stress complicate wound healing. In recent years, nanomaterials with natural enzymatic activities have enabled the development of new antibacterial pathways. In this study, Cu-FeO nanoclusters with multienzyme properties were synthesised. Interestingly, they exhibited activity similar to that of horseradish peroxidase (POD) in acidic environments but their functions resembled superoxide dismutase and catalase in neutral or weakly alkaline environments. In vitro studies have demonstrated the good free-radical scavenging activity of Cu-FeO nanoclusters in a neutral environment. Under acidic conditions, Cu-FeO nanoclusters combined with HO demonstrated good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The combination of Cu-FeO and HO was found to be effective in preventing MRSA infections and promoting wound healing in animal models. RNA sequencing (RNA-seq) technology revealed that chemodynamic therapy (CDT) using nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria, destroy the transport system on the surface of MRSA, and affect quorum sensing to hinder the formation of biofilms, thus achieving effective antibacterial efficacy. The use of Cu-FeO nanoclusters as a novel class of multi-catalytically active nanozymes in the anti-infection of disease-causing pathogens and wound healing has significant potential. STATEMENT OF SIGNIFICANCE: Cu-FeO nanoclusters with multienzyme properties were successfully prepared by a solvothermal method. Cu-FeO nanoclusters exhibited horseradish peroxidase (POD)-like activity in acidic environments and also showed synergistic effects similar to superoxide dismutase peroxidase in neutral or weakly basic environments. More importantly, these Cu-FeO nanoclusters showed high biosafety with no apparent in vivo toxicity. Chemodynamic therapy (CDT) using Cu-FeO nanoclusters was revealed by RNA sequencing (RNA-Seq) technology to interfere with the metabolic processes of MRSA bacteria, such as galactose metabolism, disrupt the MRSA surface transport system, and impede biofilm formation, resulting in effective antibacterial efficacy. The use of Cu-FeO nanoclusters for anti-infection and wound healing of pathogenic pathogens has significant potential as a novel class of multi-catalytic active nanoclusters.

摘要

感染和氧化应激会使伤口愈合变得复杂。近年来,具有天然酶活性的纳米材料开启了新的抗菌途径。在本研究中,合成了具有多种酶特性的铜铁氧化物(Cu-FeO)纳米簇。有趣的是,它们在酸性环境中表现出与辣根过氧化物酶(POD)相似的活性,但在中性或弱碱性环境中其功能类似于超氧化物歧化酶和过氧化氢酶。体外研究表明,Cu-FeO纳米簇在中性环境中具有良好的自由基清除活性。在酸性条件下,Cu-FeO纳米簇与过氧化氢(HO)结合对耐甲氧西林金黄色葡萄球菌(MRSA)和大肠杆菌(E. coli)表现出良好的抗菌活性。研究发现,Cu-FeO与HO的组合在动物模型中可有效预防MRSA感染并促进伤口愈合。RNA测序(RNA-seq)技术显示,使用纳米颗粒的化学动力学疗法(CDT)可干扰MRSA细菌中的半乳糖代谢等代谢过程,破坏MRSA表面的转运系统,并影响群体感应以阻碍生物膜的形成,从而实现有效的抗菌效果。将Cu-FeO纳米簇作为一类新型的多催化活性纳米酶用于致病病原体的抗感染和伤口愈合具有巨大潜力。重要意义声明:通过溶剂热法成功制备了具有多种酶特性的Cu-FeO纳米簇。Cu-FeO纳米簇在酸性环境中表现出类似辣根过氧化物酶(POD)的活性,在中性或弱碱性环境中也表现出类似于超氧化物歧化酶过氧化物酶的协同作用。更重要的是,这些Cu-FeO纳米簇显示出高生物安全性,在体内无明显毒性。RNA测序(RNA-Seq)技术显示,使用Cu-FeO纳米簇的化学动力学疗法(CDT)可干扰MRSA细菌的代谢过程,如半乳糖代谢,破坏MRSA表面转运系统,并阻碍生物膜形成,从而产生有效的抗菌效果。将Cu-FeO纳米簇作为一类新型的多催化活性纳米簇用于致病病原体的抗感染和伤口愈合具有巨大潜力。

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