Abstract

Nanosilver has been regarded as a promising alternative to traditional antibiotics for fighting pathogen-associated infections due to its efficacy toward a broad spectrum of pathogens. However, bacterial resistance to nanosilver has emerged recently. In this contribution, a surface engineering strategy based on N-halamine chemistry to address bacterial resistance to nanosilver was proposed. Using 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) as an N-halamine source, AgCl nanodots were deposited on the surface of Ag nanowires (Ag NWs) via in situ redox reaction to prepare AgCl-on-Ag NWs. After in vitro and in vivo tests, AgCl-on-Ag NWs effectively inactivated two antibiotic-resistant bacteria, ampicillin-resistant Escherichia coli (AREC) and methicillin-resistant Staphylococcus aureus (MRSA) with the minimum bactericidal concentration (MBC) as low as 10 μg·ml⁻¹ and exhibited good biosafety against normal cells. The experimental and theoretical tests demonstrated that AgCl-on-Ag NWs worked on AREC and MASA by generating high level of reactive oxygen species under visible light irradiation, coupled with the sustained Ag⁺ ion release. Meanwhile, the antibacterial mechanism of AgCl-on-Ag NWs against MRSA was verified at the gene level by transcriptome analysis (RNA sequencing). Moreover, the full-thickness defect model verified that AgCl-on-Ag NWs reduced inflammatory cell infiltration and dramatically accelerated wound healing. This work provides a synergistic mechanism based on nanosilver surface engineering to eradicate the resistant bacteria that can alleviate drug resistance and develop an innovative approach for the treatment of bacterial infections.

中文翻译：

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纳米银表面工程激活活性氧以治疗耐药细菌感染的皮肤组织

摘要

由于其对多种病原体的功效，纳米银被认为是对抗病原体相关感染的传统抗生素的有前途的替代品。然而，最近出现了细菌对纳米银的耐药性。在这篇文章中，提出了一种基于 N-卤胺化学的表面工程策略，以解决细菌对纳米银的耐药性。以1,3-二氯-5,5-二甲基乙内酰脲（DCDMH）为N-卤胺源，通过原位氧化还原反应将AgCl纳米点沉积在Ag纳米线（Ag NWs）表面，制备AgCl-on-Ag NWs。经过体外和体内测试，AgCl-on-Ag NWs可有效灭活两种抗生素耐药细菌，氨苄西林耐药大肠杆菌（AREC）和耐甲氧西林金黄色葡萄球菌（MRSA），最低杀菌浓度（MBC）低至10 μg·ml ^-1对正常细胞表现出良好的生物安全性。实验和理论测试表明，AgCl-on-Ag NWs 通过在可见光照射下产生高水平的活性氧以及持续的 Ag ⁺离子释放来对 AREC 和 MASA 起作用。同时，通过转录组分析（RNA测序）在基因水平验证了AgCl-on-Ag NWs对MRSA的抗菌机制。此外，全层缺损模型验证了AgCl-on-Ag NWs减少了炎症细胞浸润并显着加速了伤口愈合。这项工作提供了一种基于纳米银表面工程的协同机制来根除耐药细菌，从而减轻耐药性，并开发治疗细菌感染的创新方法。