仿DNase酶的双金属分级多孔MOFs:制备与抗细菌生物膜应用  

DNase-mimetics based on bimetallic hierarchically macroporous MOFs for the efficient inhibition of bacterial biofilm

作　　者：夏凡 李可 杨健 陈婧雯 刘熙濛 龚鸣 顾金楼 Fan Xia;Ke Li;Jian Yang;Jingwen Chen;Ximeng Liu;Ming Gong;Jinlou Gu(Key Laboratory for Ultrafine Materials of Ministry of Education,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai 200237,China)

机构地区：[1]Key Laboratory for Ultrafine Materials of Ministry of Education,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai 200237,China

出　　处：《Science China Materials》2024年第1期343-354,共12页中国科学（材料科学）（英文版）

基　　金：financially supported by the National Natural Science Foundation of China (22275054,52103314,21975072,and 51902106);Chenguang Plan of Shanghai Education Development Foundation (21CGA38);the Program of Shanghai Academic/Technology Research Leader (23XD1401000)。

摘　　要：本研究成功构建了具有切割DNA能力的双金属枝状大孔金属有机框架(MOFs;HMUiO-66(Zr/Ce)),并将其用于高效破坏生物膜并抑制细菌生长.通过改变Zr/Ce的投料比,可在0-69%的范围内精确调控Zr/Ce的引入量,并控制其粒径在1μm-150 nm之间.HMUiO-66(Zr/Ce)具有独特的化学和热稳定性,开放的大孔结构和可接近的Lewis酸活性位点,表现出模拟DNA酶活性.双金属MOFs中丰富的Zr-OH位点能有效地捕获核酸,而相邻的Ce-OH基团对磷氧键形成亲核攻击,协同放大DNA的水解速率,使得开发的HMUiO-66(Zr/Ce)能够作为切割细胞外DNA和清除细菌生物膜的纳米药物.在此基础上,我们设计了一种仿生HMUiO-66(Zr/Ce)/PVDF膜,该生物膜可抑制细菌粘附和定植,在抗菌治疗和医疗器械中具有广阔的应用前景.The accumulation of pathogenic biofilms poses a serious threat to human health,making their effective de-struction and eradication significant,yet greatly challenging.Herein,the bimetallic hierarchically macroporous metal-or-ganic frameworks(MOFs)(HMUiO-66(Zr/Ce))with ability to cleave DNA were successfully constructed for the efficient destruction of biofilm and thus inhibition of bacterial growth.By systematically adjusting the feed ratios of Zr/Ce,their particle size could be minimized to approximately 150 nm and the amount of Zr introduced into HMUiO-66(Zr/Ce)could be precisely tailored over a broad molar range from 0 to 69%.The developed HMUiO-66(Zr/Ce)feature unique chemical and thermal stabilities as well as abundant exposed Lewis acid sites.Benefitting from their open macroporous structure and accessible active sites,they exhibit exceptional DNase-mimetic activities.The abundant Zr-OH sites present in bimetallic MOFs could effectively sequester nucleic acids,while adjacent Ce-OH moieties form nucleophilic attacks toward phos-phorus-oxygen bonds,synergistically amplifying the hydro-lysis rate of DNA.Such a unique DNA cleavage ability makes the developed HMUiO-66(Zr/Ce)competent to serve as na-nomedicines for cleaving cross-linked extracellular DNA and eradicating bacterial biofilms.On this basis,we designed a biomimetic HMUiO-66(Zr/Ce)/polyvinylidene difluoride(PVDF)film which could discernibly suppress bacterial ad-herence and colonization,prefiguring their broad application potentials in antimicrobial therapy and medical devices.

关 键 词：金属有机框架 细菌生物膜 双金属 医疗器械 水解速率 细菌粘附 PVDF膜 大孔结构 

分 类 号：TB383.2[一般工业技术—材料科学与工程] R318[医药卫生—生物医学工程]