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具有增强纳米酶活性的卤素阴离子调控金属有机框架用于破坏细菌生物膜

Halogen anion modulated metal-organic frameworks with enhanced nanozyme activities for bacterial biofilm disruption.

作者信息

Ge Tianjin, Wu Renfei, Yu Tianrong, Hasan Muhammad Sajjad Ul, Liu Jian

机构信息

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Joint International Research Laboratory of Carbon-Based Materials and Devices, Soochow University, 199 Ren'ai Rd, Suzhou 215123, Jiangsu, P. R. China.

出版信息

Nanoscale. 2025 Apr 17;17(16):9963-9973. doi: 10.1039/d5nr00131e.

DOI:10.1039/d5nr00131e
PMID:40145893
Abstract

There is an urgent need to develop new nanozymes with enhanced catalytic activities to combat bacterial infections, which have become increasingly challenging due to the misuse of antibiotics and the difficulties of new antibiotic discovery. Here, we employed a new strategy against bacterial biofilms by introducing halide anions to modulate the crystal facets of ZIF-L metal-organic frameworks (MOFs) and then loading chloroquine to form Ch@ZIF-L. The modulation of crystal facets significantly enhanced the oxidase activities of ZIF-L, which can be significantly changed by modulation of its crystal facets, with the hexagonal ZIF-L (ZIF-L-H-Cl) structure showing the highest oxidase activity. At pH 6.0, over 80% of chloroquine was released from Ch@ZIF-L-H-Cl within 8 hours, altering the DNA conformation of bacterial biofilms and disrupting the extracellular polymeric substances (EPSs). The generation of singlet oxygen catalyzed by ZIF-L-H-Cl can effectively kill bacteria at the infected wound site. The composite nanozyme of Ch@ZIF-L-H-Cl, when treated at 100 μg mL, exhibited no adverse effects on normal cell growth or hemolysis. Our experiments demonstrated an 85% reduction of the wound area by day 8 and a rapid recovery of body weight in mice with wounds infected with () biofilms. Furthermore, substantial reductions in bacterial counts were observed in both wounds and blood samples in the mice, highlighting the great potential of Ch@ZIF-L-H-Cl in combating bacterial biofilm infections.

摘要

由于抗生素的滥用以及新抗生素发现的困难,对抗细菌感染变得越来越具有挑战性,因此迫切需要开发具有增强催化活性的新型纳米酶。在此,我们采用了一种针对细菌生物膜的新策略,即引入卤化物阴离子来调节ZIF-L金属有机框架(MOF)的晶面,然后负载氯喹以形成Ch@ZIF-L。晶面的调节显著增强了ZIF-L的氧化酶活性,其氧化酶活性可通过调节晶面而显著改变,其中六方ZIF-L(ZIF-L-H-Cl)结构显示出最高的氧化酶活性。在pH 6.0时,超过80%的氯喹在8小时内从Ch@ZIF-L-H-Cl中释放出来,改变了细菌生物膜的DNA构象并破坏了细胞外聚合物(EPS)。ZIF-L-H-Cl催化产生的单线态氧可有效杀死感染伤口部位的细菌。当以100μg/mL处理时,Ch@ZIF-L-H-Cl复合纳米酶对正常细胞生长或溶血没有不良影响。我们的实验表明,在感染()生物膜的小鼠中,到第8天时伤口面积减少了85%,体重迅速恢复。此外,在小鼠的伤口和血液样本中均观察到细菌数量大幅减少,突出了Ch@ZIF-L-H-Cl在对抗细菌生物膜感染方面的巨大潜力。

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