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一种具有协同增强细菌抑制作用的金属卟啉和乙内酰脲功能化纳米酶。

A metalloporphyrin and hydantoin functionalized nanozyme with synergistically enhanced bacterial inhibition.

作者信息

Li Yanhong, Wang Quanbo, Qu Xinyan, Zhang Qiang, Zhang Xiaomei

机构信息

School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China.

School of Pharmaceutical Sciences, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China.

出版信息

Biomater Sci. 2023 Feb 28;11(5):1785-1796. doi: 10.1039/d2bm01337a.

Abstract

An elaborate design of multimodal antibacterial agents has been revealed to be a promising strategy to address bacterial resistance, originating from the abuse of antibiotics. In this work, we have developed a positively charged and porous material, FePPOP, as a disinfectant introducing 1,3-dibromo-5,5-dimethylhydantoin (Hydantoin) and porphyrin iron units into a polymer framework. The extended π conjugated networks of FePPOP endowed the material with strong near-infrared (NIR) absorption, high density of surface catalytic active centers, superior stability, and reproducibility. FePPOP exhibits high peroxidase mimetic and photo-Fenton activity, which can catalyze the biologically allowable maximum concentrations of hydrogen peroxide (100 μM) to produce a vast amount of hydroxyl radicals. Simultaneously, the effective electrostatic interaction between the positively charged FePPOP and the negatively charged bacteria facilitates the binding of FePPOP on the bacterial membrane, restricting bacteria within the destruction range of hydroxyl radicals and thus making the bacteria more vulnerable. Finally, further close contact between bacteria and Hydantoin units in FePPOP gave the material an antibacterial efficiency of over 99.999%. Compared with chemical therapy, photo-Fenton therapy, or peroxidase catalytic therapy alone, FePPOP had a noteworthy multi-amplified antibacterial efficiency. Furthermore, FePPOP exhibited good biocompatibility and negligible cytotoxicity. The antibacterial therapy on the () infected mouse wound model clearly proved the effectiveness of FePPOP for fighting bacterial infections. This work highlights opportunities for the design of nanozymes with enhanced bacteriostatic activity, providing a new avenue for the construction of novel antibiotics.

摘要

多模态抗菌剂的精心设计已被证明是解决因抗生素滥用而产生的细菌耐药性的一种有前景的策略。在这项工作中,我们开发了一种带正电荷的多孔材料FePPOP作为消毒剂,将1,3 - 二溴 - 5,5 - 二甲基乙内酰脲(乙内酰脲)和卟啉铁单元引入聚合物骨架中。FePPOP的扩展π共轭网络赋予该材料强烈的近红外(NIR)吸收、高密度的表面催化活性中心、卓越的稳定性和可重复性。FePPOP表现出高过氧化物酶模拟活性和光芬顿活性,可催化生物允许的过氧化氢最大浓度(100 μM)产生大量羟基自由基。同时,带正电荷的FePPOP与带负电荷的细菌之间有效的静电相互作用促进了FePPOP在细菌膜上的结合,将细菌限制在羟基自由基的破坏范围内,从而使细菌更易受到攻击。最后,细菌与FePPOP中的乙内酰脲单元进一步紧密接触使该材料具有超过99.999%的抗菌效率。与单独的化学疗法、光芬顿疗法或过氧化物酶催化疗法相比,FePPOP具有显著的多倍增强抗菌效率。此外,FePPOP表现出良好的生物相容性和可忽略不计的细胞毒性。对()感染的小鼠伤口模型进行的抗菌治疗清楚地证明了FePPOP对抗细菌感染的有效性。这项工作突出了设计具有增强抑菌活性的纳米酶的机会,为构建新型抗生素提供了一条新途径。

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