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

仿DNase酶的双金属分级多孔MOFs: 制备与抗细菌 生物膜应用

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Abstract

The accumulation of pathogenic biofilms poses a serious threat to human health, making their effective destruction and eradication significant, yet greatly challenging. Herein, the bimetallic hierarchically macroporous metal-organic 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 phosphorus–oxygen bonds, synergistically amplifying the hydrolysis rate of DNA. Such a unique DNA cleavage ability makes the developed HMUiO-66(Zr/Ce) competent to serve as nanomedicines 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 adherence and colonization, prefiguring their broad application potentials in antimicrobial therapy and medical devices.

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1 μm–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.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (22275054, 52103314, 21975072, and 51902106), Chenguang Plan of Shanghai Education Development Foundation (21CGA38), and the Program of Shanghai Academic/Technology Research Leader (23XD1401000).

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Authors and Affiliations

  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

    Fan Xia  (夏凡), Ke Li  (李可), Jian Yang  (杨健), Jingwen Chen  (陈婧雯), Ximeng Liu  (刘熙濛), Ming Gong  (龚鸣) & Jinlou Gu  (顾金楼)

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  1. Fan Xia  (夏凡)
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  2. Ke Li  (李可)
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  3. Jian Yang  (杨健)
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  4. Jingwen Chen  (陈婧雯)
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  5. Ximeng Liu  (刘熙濛)
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  6. Ming Gong  (龚鸣)
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  7. Jinlou Gu  (顾金楼)
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Contributions

Author contributions Yang J and Gu J designed the project and acquired the funding. Xia F conducted the experiments, and performed the data analysis and interpretation. Chen J, Liu X, and Gong M assisted during the experiments and data analysis. Li K and Yang J supported the data interpretation. Xia F and Gu J wrote and modified the manuscript with input from all authors.

Corresponding authors

Correspondence to Jian Yang  (杨健) or Jinlou Gu  (顾金楼).

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Conflict of interest The authors declare that they have no conflict of interest.

Additional information

Supplementary information Experimental details and supporting data are available in the online version of this paper.

Fan Xia received her Master’s degree from Yangzhou University in 2021. Currently, she is a PhD candidate at East China University of Science and Technology (ECUST). Her current research interests focus on the construction of hierarchically porous MOFs for biomedical applications.

Jian Yang received his PhD degree from ECUST in 2018 and currently is an associate researcher at the Key Laboratory for Ultrafine Materials of Ministry of Education. His research interests focus on the design and construction of hierarchically porous MOFs for biocatalysis, biosensor, and imaging applications.

Jinlou Gu received his PhD degree in material physics and chemistry from Shanghai Institute of Ceramic, Chinese Academy of Sciences in 2005. Then, he worked as a postdoctoral fellow at The Chinese University of Hong Kong, University of Tokyo and Keele University from 2005 to 2008. Currently, he is a full professor at ECUST. His research focuses on the construction of porous materials and their applications in biosensing, biological separation, and biomimetic catalysis.

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Xia, F., Li, K., Yang, J. et al. DNase-mimetics based on bimetallic hierarchically macroporous MOFs for the efficient inhibition of bacterial biofilm. Sci. China Mater. 67, 343–354 (2024). https://doi.org/10.1007/s40843-023-2687-7

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  • DOI: https://doi.org/10.1007/s40843-023-2687-7

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