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Microwave-Responsive Nanoplatform with Robust ROS Generation and Inhibiting Effects of Two-Component System and Quorum Sensing for the Treatment of MRSA-Induced Osteomyelitis
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2024-07-01 , DOI: 10.1002/adfm.202405421
Hao Cheng 1, 2 , Yongqiang Yang 3 , Yueyue Wang 2 , Jiqiang Guo 1, 4 , Xiong Jiao 1 , Di Huang 1 , Meiwen An 1 , Xiaohong Yao 2 , Paul K. Chu 5 , Xiangyu Zhang 1, 2
Affiliation  

The hypoxic environment of deep tissue and the weak energy of microwave (MW) are still the major limitations of MW catalytic therapy. In this work, an MW-responsive nano-platform consisting of an Mn-doped porphyrin metal–organic framework loaded with calcium peroxide (Mn0.1PCC) is designed to regulate the microenvironment of the injection site and enhance the generation of reactive oxygen species. The excellent MW absorbing properties of Mn0.1PCC improve the Fenton reaction between hydrogen peroxide formed by the hydrolysis of calcium peroxide and released Mn2+ generating more hydroxyl radicals under MW. This process does not consume the oxygen substrate and even produces oxygen to improve the hypoxic environment. Therefore, at a low and safe concentration (125 µg mL−1), the antibacterial rate of Mn0.1PCC against 4 × 108 CFU mL−1 of methicillin-resistant Staphylococcus aureus (MRSA) after MW irradiation for 15 min is 99.71% ± 0.18%. Mn0.1PCC, upon exposure to MW, prevents the recurrence of bacterial infections and overcomes drug resistance by inhibiting quorum sensing and the two-component system of MRSA. It can also induce macrophage M1 polarization, up-regulate the pro-inflammatory factor tumor necrosis factor-α, and enhance the phagocytosis of macrophage to bacteria. This strategy provides insights into the development of high-performance MW-responsive nanocomposites for the treatment of infections in deep tissues.

中文翻译:


微波响应纳米平台具有强大的 ROS 生成和双组分系统抑制作用以及群体感应,用于治疗 MRSA 引起的骨髓炎



深部组织的缺氧环境和微波(MW)能量较弱仍然是微波催化治疗的主要局限性。在这项工作中,由负载过氧化钙(Mn 0.1 PCC)的锰掺杂卟啉金属有机框架组成的MW响应纳米平台旨在调节注射部位的微环境并增强注射部位的微环境。活性氧的产生。 Mn 0.1 PCC优异的MW吸收性能改善了过氧化钙水解形成的过氧化氢与释放的Mn 2+ 之间的Fenton反应,在MW下产生更多的羟基自由基。该过程不消耗氧底物,甚至产生氧气,改善缺氧环境。因此,在低安全浓度(125 µg mL −1 )下,Mn 0.1 PCC 对 4 × 10 8 CFU mL −1 MW照射15分钟后耐甲氧西林金黄色葡萄球菌(MRSA)的检出率为99.71%±0.18%。 Mn 0.1 PCC 在暴露于 MW 后,可通过抑制群体感应和 MRSA 的双组分系统来防止细菌感染的复发并克服耐药性。它还可以诱导巨噬细胞M1极化,上调促炎因子肿瘤坏死因子-α,增强巨噬细胞对细菌的吞噬作用。该策略为开发用于治疗深层组织感染的高性能微波响应纳米复合材料提供了见解。
更新日期:2024-07-01
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