biostudies-literatureWu RMinistry of Science and Technology of the People&apos;s Republic of ChinaUniversitair Medisch Centrum GroningenCollaborative Innovation Center of Suzhou Nano Science and TechnologySuzhou Key Laboratory of Nanotechnology and Biomedicine, Institute of Functional Nano and Soft Materials, Soochow UniversityNational Natural Science Foundation of ChinaJoint International Research Laboratory of Carbon-Based Materials and DevicesHigher Education Discipline Innovation Project2328-2340https://www.ebi.ac.uk/biostudies/studies/S-EPMC9933606biostudies-literatureUnknown17(3)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 <i>Staphylococcus aureus</i> 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.ACS nanoA Heterocatalytic Metal-Organic Framework to Stimulate Dispersal and Macrophage Combat with Infectious Biofilms.PMC99336062017YFE013170021874096Liu JShi RJiang GRen YWu RYu TLiu Svan der Mei HCBusscher HJfalseA Heterocatalytic Metal-Organic Framework to Stimulate Dispersal and Macrophage Combat with Infectious Biofilms.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 <i>Staphylococcus aureus</i> 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.2023-01-01T00:00:00Z2023 Feb2024-11-20T00:15:57.939Z2024-11-20T00:15:57.939ZS-EPMC99336063669208110.1021/acsnano.2c09008