Abstract：
Eradication of infectious biofilms is becoming increasingly difficult due to the growing number of antibiotic-resistant strains. This necessitates development of nonantibiotic-based, antimicrobial approaches. To this end, we designed a heterocatalytic metal-organic framework composed of zirconium 1,4-dicarboxybenzene (UiO-66) with immobilized Pt nanoparticles (Pt-NP/UiO-66). Pt-NP/UiO-66 enhanced singlet-oxygen generation compared with Pt nanoparticles or UiO-66, particularly in an acidic environment. Singlet-oxygen generation degraded phosphodiester bonds present in eDNA gluing biofilms together and therewith dispersed biofilms. Remaining biofilms possessed a more open structure. Concurrently, Pt-NP/UiO-66 stimulated macrophages to adapt a more M1-like, \"fighting\" phenotype, moving faster toward their target bacteria and showing increased bacterial killing. As a combined effect of biofilm dispersal and macrophage polarization, a subcutaneous Staphylococcus aureus biofilm in mice was more readily eradicated by Pt-NP/UiO-66 than by Pt nanoparticles or UiO-66. Therewith, heterocatalytic Pt-NP/UiO-66 metal-organic frameworks constitute a nonantibiotic-based strategy to weaken protective matrices and disperse infectious biofilms, while strengthening macrophages in bacterial killing.
摘要：
由于抗生素抗性菌株的数量不断增加,感染性生物膜的根除变得越来越困难。这需要开发基于非抗生素的，抗菌方法。为此,我们设计了一种由1,4-二羧基苯锆（UiO-66）和固定的Pt纳米颗粒（Pt-NP/UiO-66）组成的异催化金属有机框架。与Pt纳米颗粒或UiO-66相比,Pt-NP/UiO-66增强了单态氧的产生,特别是在酸性环境中。单线态氧产生将存在于eDNA中的降解的磷酸二酯键将生物膜胶合在一起并由此分散的生物膜。剩余的生物膜具有更开放的结构。同时,Pt-NP/UiO-66刺激巨噬细胞适应更多的M1样，“战斗”表型，向目标细菌移动得更快，并显示出增加的细菌杀伤能力。作为生物膜扩散和巨噬细胞极化的综合作用，小鼠皮下金黄色葡萄球菌生物膜比Pt纳米颗粒或UiO-66更容易被Pt-NP/UiO-66根除。因此，异质催化的Pt-NP/UiO-66金属-有机骨架构成了一种非基于抗生素的策略，可削弱保护性基质并分散感染性生物膜，同时加强巨噬细胞对细菌的杀伤。
