Abstract：
Drug-resistant bacterial infections cause significant harm to public life, health, and property. Biofilm is characterized by overexpression of glutathione (GSH), hypoxia, and slight acidity, which is one of the main factors for the formation of bacterial resistance. Traditional antibiotic therapy gradually loses its efficacy against multi-drug-resistant (MDR) bacteria. Therefore, synergistic therapy, which regulates the biofilm microenvironment, is a promising strategy. A multifunctional nanoplatform, SnFe2O4-PBA/Ce6@ZIF-8 (SBC@ZIF-8), in which tin ferrite (SnFe2O4, denoted as SFO) as the core, loaded with 3-aminobenzeneboronic acid (PBA) and dihydroporphyrin e6 (Ce6), and finally coated with zeolite imidazole salt skeleton 8 (ZIF-8). The platform has a synergistic photothermal therapy (PTT)/photodynamic therapy (PDT) effect, which can effectively remove overexpressed GSH by glutathione peroxidase-like activity, reduce the antioxidant capacity of biofilm, and enhance PDT. The platform had excellent photothermal performance (photothermal conversion efficiency was 55.7 %) and photothermal stability. The inhibition rate of two MDR bacteria was more than 96 %, and the biofilm clearance rate was more than 90 % (150 μg/mL). In the animal model of MDR S. aureus infected wound, after 100 μL SBC@ZIF-8+NIR (150 μg/mL) treatment, the wound area of mice was reduced by 95 % and nearly healed. The serum biochemical indexes and H&E staining results were within the normal range, indicating that the platform could promote wound healing and had good biosafety. In this study, we designed and synthesized multifunctional nanoplatforms with good anti-drug-resistant bacteria effect and elucidated the molecular mechanism of its anti-drug-resistant bacteria. It lays a foundation for clinical application in treating wound infection and promoting wound healing.
摘要：
耐药细菌感染对公众生活造成重大危害,健康,和财产。生物膜的特征是谷胱甘肽（GSH）的过表达，缺氧,和轻微的酸度，是形成细菌耐药性的主要因素之一。传统的抗生素治疗逐渐失去对多重耐药（MDR）细菌的功效。因此,协同治疗,调节生物膜微环境，是一个很有前途的策略。多功能纳米平台，SnFe2O4-PBA/Ce6@ZIF-8(SBC@ZIF-8),其中铁酸锡（SnFe2O4，表示为SFO）作为核心，负载3-氨基苯硼酸（PBA）和二氢卟啉e6（Ce6），最后用沸石咪唑盐骨架8(ZIF-8)涂覆。该平台具有协同光热疗法（PTT）/光动力疗法（PDT）的作用，可以通过谷胱甘肽过氧化物酶样活性有效去除过表达的GSH，降低生物膜的抗氧化能力，并增强PDT。该平台具有优异的光热性能(光热转换效率为55.7%)和光热稳定性。两种MDR菌的抑菌率均在96%以上，生物膜清除率达90%以上(150μg/mL)。在MDR金黄色葡萄球菌感染伤口的动物模型中,100μLSBC@ZIF-8+NIR（150μg/mL）处理后，小鼠的伤口面积减少了95％，几乎愈合。血清生化指标及H&E染色结果均在正常范围内,说明该平台能促进创面愈合,具有良好的生物安全性。在这项研究中,我们设计并合成了具有良好抗耐药细菌作用的多功能纳米平台，并阐明了其抗耐药细菌的分子机制。为临床应用于治疗创面感染和促进创面愈合奠定了基础。
