A heterocatalytic metal-organic-framework to stimulate dispersal and macrophage combat with infectious biofilms
Renfei Wu1,2, Tianrong Yu1,2, Sidi Liu1,2, Rui Shi1,2, Guimei Jiang1,2, Yijin Ren3, Henny C. van der Mei2*, Henk J. Busscher2*, and Jian Liu1*
1Institute of Functional Nano and Soft Materials (FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Joint International Research Laboratory of Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, P. R. China
2University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, 9713 AV Groningen, The Netherlands
3University of Groningen and University Medical Center of Groningen, Department of Orthodontics, 9700 RB Groningen, The Netherlands
Eradication of infectious biofilms is becoming increasingly difficult due to the growing number of antibiotic-resistant strains. This necessitates development of nonantibiotic-based, antimicrobial approaches. To this end, we designed a heterocatalytic metal−organic framework composed of zirconium 1,4-dicarboxybenzene (UiO-66) with immobilized Pt nanoparticles (Pt-NP/UiO-66). Pt-NP/UiO-66 enhanced singlet-oxygen generation compared with Pt nanoparticles or UiO-66, particularly in an acidic environment. Singlet-oxygen generation degraded phosphodiester bonds present in eDNA gluing biofilms together and therewith dispersed biofilms. Remaining biofilms possessed a more open structure. Concurrently, Pt-NP/UiO-66 stimulated macrophages to adapt a more M1-like, “fighting” phenotype, moving faster toward their target bacteria and showing increased bacterial killing. As a combined effect of biofilm dispersal and macrophage polarization, a subcutaneous Staphylococcus aureus biofilm in mice was more readily eradicated by Pt-NP/UiO-66 than by Pt nanoparticles or UiO-66. Therewith, heterocatalytic Pt-NP/UiO-66 metal−organic frameworks constitute a nonantibiotic-based strategy to weaken protective matrices and disperse infectious biofilms, while strengthening macrophages in bacterial killing.