Abstract：
Recently, chloroperoxidase (CPO)-mediated enzyme dynamic therapy (EDT) by mimicking the antipathogen function of neutrophils via generating highly active signet oxygen (1O2) has attracted great interest in biomedical applications. However, the therapeutic efficiency of EDT is largely restricted by the low CPO delivery efficiency and insufficient hydrogen peroxide (H2O2) supply. In the present work, a neutrophil-mimicking nanozyme of MGBC with high CPO delivery efficiency, H2O2 self-supply, and enzyme-cascade catalytic properties is designed for high-efficient treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. In the infection microenvironment, MGBC can effectively catalyze glucose to self-supply substantial H2O2, which enables long-lasting 1O2 generation via the CPO-mediated catalytic reaction. At the meantime, MGBC can also catalyze H2O2 to sustainably release NO for gas therapy (GT), which synergistically strengthens the therapeutic effect of EDT. As a result, MGBC displayed effective MRSA-killing and MSRA biofilms-eradicating properties, and high efficiency in treating both MRSA infected full-thickness excision wounds and subcutaneous MRSA infection by exerting the synergistic bimodal EDT/GT therapeutic effects. In-depth mechanism study revealed that the synergistic EDT/GT antibacterial effects of MGBC can attenuate the drug resistance and toxicity of MRSA by significantly downregulating quorum sensing, multidrug efflux, virulence, and biofilm formation-related genes.
摘要：
最近,氯过氧化物酶（CPO）介导的酶动态疗法（EDT）通过产生高活性印戒氧（1O2）来模拟中性粒细胞的抗病原体功能，在生物医学应用中引起了极大的兴趣。然而,EDT的治疗效率在很大程度上受到低CPO递送效率和过氧化氢(H2O2)供应不足的限制。在目前的工作中,具有高CPO递送效率的MGBC的中性粒细胞模拟纳米酶，H2O2自供,和酶级联催化特性设计用于高效治疗耐甲氧西林金黄色葡萄球菌（MRSA）感染。在感染微环境中，MGBC可以有效地催化葡萄糖自我供应大量的H2O2,这使得能够通过CPO介导的催化反应持久地产生1O2。同时,MGBC还可以催化H2O2持续释放NO用于气体治疗（GT），协同增强EDT的治疗效果。因此,MGBC显示出有效的MRSA杀伤和MSRA生物膜根除特性，通过发挥协同的双峰EDT/GT治疗作用，可以有效治疗MRSA感染的全层切除伤口和皮下MRSA感染。深入的机制研究表明，MGBC的协同EDT/GT抗菌作用可以通过显著下调群体感应来减弱MRSA的耐药性和毒性。多药外排，毒力,和生物膜形成相关基因。
