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

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.