title: One-pot synthesis of multifunctional nanoscale metal-organic frameworks as an effective antibacterial agent against multidrug-resistant Staphylococcus aureus.
abstract: Drug-resistant bacteria are an increasingly serious threat to global public health. In particular, infections from multidrug-resistant (MDR) Gram-positive bacteria (i.e. Staphylococcus aureus) are growing global health concerns. In this work, we report the first use of nanoscale metal-organic frameworks (NMOFs) coencapsulating an antibiotic (vancomycin) and targeting ligand (folic acid) in one pot to enhance therapeutic efficacy against MDR S. aureus. Zeolitic imidazolate framework (ZIF-8) NMOFs, which have globular morphologies coencapsulating vancomycin and folic acid, are characterized by transmission electron microscopy, field-emission scanning electron microscopy, powder x-ray diffraction, ulltraviolet-visible spectroscopy, and dynamic light-scattering techniques. We determined that the presence of folic acid on the surface of the NMOFs is significant in the sense of effective uptake by MDR S. aureus through endocytosis. The functionalized NMOFs transport vancomycin across the cell wall of MDR S. aureus and enhance antibacterial activity, which has been confirmed from studies of the minimum inhibitory concentration, minimum bactericidal concentration, cytotoxicity of bacterial cells, and generation of reactive oxygen species. This work shows that functionalized NMOFs hold great promise for effective treatment of MDR S. aureus.
authors.affiliation: Department of Applied Chemistry, Indian Institute of Technology (ISM), Dhanbad-826004, Jharkhand, India.
authors.forename: Angshuman Ray
authors.initials: AR
authors.lastname: Chowdhuri
authors.forename: Balaram
authors.initials: B
authors.lastname: Das
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Satyajit
authors.initials: S
authors.lastname: Tripathy
authors.forename: Somenath
authors.initials: S
authors.lastname: Roy
authors.forename: Sumanta Kumar
authors.initials: SK
authors.lastname: Sahu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D000067493:Dynamic Light Scattering; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D005492:Folic Acid / Q000494:pharmacology; D042541:Intracellular Space / Q000378:metabolism; D049449:Luminescence; D000073396:Metal-Organic Frameworks / Q000138:chemical synthesis* / Q000737:chemistry; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D014640:Vancomycin / Q000494:pharmacology; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D000073396:Metal-Organic Frameworks; D017382:Reactive Oxygen Species; D014640:Vancomycin; D005492:Folic Acid