Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Small. 2023 Aug;19(35):e2300199. doi: 10.1002/smll.202300199. Epub 2023 May 8.
Bacterial infections pose a significant threat to global public health; therefore, the development of novel therapeutics is urgently needed. Herein, a controllable antibacterial nanoplatform utilizing cyclodextrin metal-organic frameworks (CD-MOFs) as a template to synthesize ultrafine silver nanoparticles (Ag NPs) in their porous structure is constructed. Subsequently, polydopamine (PDA) is encapsulated on the CD-MOFs' surface via dopamine polymerization to enhance the water stability and enable hyperthermia capacity. The resulting Ag@MOF@PDA generates localized hyperthermia and gradually releases Ag to achieve long-term photothermal-chemical bactericidal capability. The release rate of Ag can be accelerated by NIR-mediated heating in a controllable manner, quickly reaching the effective concentration and reducing the frequency of medication to avoid potential toxicity. In vitro experiments demonstrate that the combined antibacterial strategy can not only effectively kill both gram-negative and gram-positive bacteria, but also directly eradicate mature biofilms. In vivo results confirm that both bacterial- and biofilm-infected wounds treated with a combination of Ag@MOF@PDA and laser exhibit satisfactory recovery with minimal toxicity, displaying a superior therapeutic effect compared to other groups. Together, the results warrant that the Ag@MOF@PDA realizes synergistic antibacterial capacity and controllable release of Ag to combat bacterial and biofilm infections, providing a potential antibiotic-free alternative in the "post-antibiotic era."
细菌感染对全球公共健康构成重大威胁;因此,迫切需要开发新的治疗方法。在此,构建了一种利用环糊精金属-有机骨架 (CD-MOF) 作为模板在其多孔结构中合成超细微银纳米粒子 (Ag NPs) 的可控抗菌纳米平台。随后,通过多巴胺聚合将聚多巴胺 (PDA) 包裹在 CD-MOFs 表面,以提高水稳定性并赋予其热疗能力。所得的 Ag@MOF@PDA 产生局部热疗并逐渐释放 Ag 以实现长期光热化学杀菌能力。Ag 的释放率可以通过 NIR 介导的加热以可控的方式加速,迅速达到有效浓度并减少用药频率以避免潜在毒性。体外实验表明,联合抗菌策略不仅可以有效杀死革兰氏阴性菌和革兰氏阳性菌,还可以直接消除成熟的生物膜。体内结果证实,Ag@MOF@PDA 与激光联合治疗细菌和生物膜感染的伤口均具有令人满意的恢复效果,毒性最小,与其他组相比具有更好的治疗效果。总之,结果表明 Ag@MOF@PDA 实现了协同抗菌能力和 Ag 的可控释放,可有效对抗细菌和生物膜感染,为“后抗生素时代”提供了一种潜在的无抗生素替代方案。