Wu Renfei, Ge Tianjin, Yu Tianrong, Shi Qiaolan, Shi Rui, Ren Yijin, Busscher Henk J, Liu Jian, van der Mei Henny C
Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
Department of Biomaterials and Biomedical Technology, University of Groningen and University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
ACS Appl Mater Interfaces. 2025 Jun 4;17(22):32111-32126. doi: 10.1021/acsami.5c08974. Epub 2025 May 21.
The era of relying on antibiotics for curing bacterial infections is rapidly approaching an end, necessitating development of non-antibiotic-based infection-control strategies. Dispersal of infectious biofilms is a potential strategy but yields dispersed bacteria in blood that may cause sepsis. We report a bromide-loaded, core-shell ZnO-nanoparticle/Ce-based metal-organic framework (ZnO@CeMOF/Br) of which the ZnO core degrades at pH ≤ 6.5, leaving the MOF's Ce node intact. ZnO-core degradation initially generates a nonradical, relatively stable, low-oxidative hydrogen peroxide that can cleave matrix DNA causing dispersal of biofilms and reacts with bromide ions to form transient hypobromous acid. Hypobromous acid modulates macrophage polarization toward an M1-like phenotype to clear dispersed bacteria from blood. Subsequently the Ce/Ce redox couple forming the Ce node acts as an electron shuttle upon oxidation/reduction to faciltate two catalytic reactions, maintaining hydrolysis of phosphodiester bonds and associated cleavage of matrix DNA as well as modulation of macrophage polarization. Neither growth of tissue cells or macrophages nor hemolysis are negatively affected by exposure to ZnO@CeMOF/Br nanocatalysts at a ZnO nanoparticle over CeMOFs weight ratio ≤ 1.2, up until CeMOF concentrations less than at least 180 μg/mL. Under biosafe, low-turnover catalytic conditions, irrigation of infected wounds in diabetic mice with ZnO@CeMOF/Br nanocatalysts (90 μg/mL) results in 100% survival, fast recovery of healthy body temperature and weight, lower numbers of CFUs in blood and wound and organ tissues, and macrophage polarization toward an M1-like phenotype, demonstrating potential of ZnO@CeMOF/Br nanocatalysts for non-antibiotic-based infection control.
依靠抗生素治疗细菌感染的时代正在迅速走向终结，因此有必要开发基于非抗生素的感染控制策略。传染性生物膜的分散是一种潜在策略，但会在血液中产生可能导致败血症的分散细菌。我们报道了一种负载溴化物的核壳结构氧化锌纳米颗粒/铈基金属有机框架（ZnO@CeMOF/Br），其中氧化锌核在pH≤6.5时降解，而金属有机框架的铈节点保持完整。氧化锌核的降解最初会产生一种非自由基、相对稳定、低氧化性的过氧化氢，它可以切割基质DNA导致生物膜分散，并与溴离子反应形成瞬时次溴酸。次溴酸可调节巨噬细胞向M1样表型极化，以清除血液中的分散细菌。随后，形成铈节点的Ce/Ce氧化还原对在氧化/还原时充当电子穿梭体，促进两个催化反应，维持磷酸二酯键的水解以及相关的基质DNA切割，以及巨噬细胞极化的调节。在氧化锌纳米颗粒与金属有机框架的重量比≤1.2且金属有机框架浓度至少低于180μg/mL之前，暴露于ZnO@CeMOF/Br纳米催化剂不会对组织细胞或巨噬细胞的生长以及溶血产生负面影响。在生物安全、低周转率的催化条件下，用ZnO@CeMOF/Br纳米催化剂（90μg/mL）冲洗糖尿病小鼠的感染伤口，可实现100%的存活率、快速恢复健康体温和体重、降低血液、伤口和器官组织中的菌落形成单位数量，并使巨噬细胞向M1样表型极化，这证明了ZnO@CeMOF/Br纳米催化剂在基于非抗生素的感染控制方面的潜力。
