Antibacterial Countermeasures via Metal–Organic Framework-Supported Sustained Therapeutic Release

Abstract

Long-term antimicrobial therapies are necessary to treat infections caused by virulent intracellular pathogens, including biothreat agents. Current treatment plans include injectable therapeutics given multiple times daily over a period for up to 8 weeks. Here, we present a metal−organic framework (MOF), zeolitic imidazolate framework-8 (ZIF-8), as a robust platform to support the sustained release of ceftazidime, an important antimicrobial agent for many critical bacterial infections. Detailed material characterization confirms the successful encapsulation of ceftazidime within the ZIF-8 matrix, indicating sustained drug release for up to a week. The antibacterial properties of ceftazidime@ZIF-8 particles were confirmed against Escherichia coli, chosen here as a representative of Gram-negative bacteria infection model in a proof-of-concept study. Further, we showed that this material system is compatible with macrophage and lung epithelial cell lines, relevant targets for antibacterial therapy for pulmonary and intracellular infections. A promising methodology to enhance the treatment of intracellular infections is to deliver the antibiotic cargo intracellularly. Importantly, this is the first study to unequivocally demonstrate direct MOF particle internalization using confocal microscopy via 3D reconstructions of z-stacks, taking advantage of the intrinsic emission properties of ZIF-8. This is an important development as it circumvents the need to use any staining dyes and addresses current methodology limitations concerning false impression of cargo uptake in the event of the carrier particle breakdown within biological media.

Metal–Organic Frameworks for Biomedical Applications

“…MOF‐based antimicrobial nanoplatforms generally contain one or more of the following features: 1) metal nodes in MOFs (such as Ag, Cu, Ni, Zn, etc.) exhibiting antibacterial activity that could undergo sustained release during the degradation of MOFs to achieve high effective antibacterial effect,56 2) the excellent containment of antimicrobial molecules based on the high surface areas and adjustable pore sizes of MOFs,57 3) the organic linkers used to build the MOF scaffolds, such as porphyrin derivatives, offering a potential to combine PDT for bacterial infections,58 4) flexible post‐modification methods that promote the further functionalization of MOFs 59. In this part, we will introduce the application progress of MOF‐based nanoplatforms in antibacterial field.…”

“…Particularly, the good dispersibility and biocompatibility of NMOFs ensure the biosecurity for in vivo applications. [7] In this review article, we will summarize the recent developments of MOF-based composite materials including the synthesis and functionalization [8][9][10][11][12][13][14][15] and their biomedical applications in the delivery of cargos including drugs, nucleic acids, proteins, and dyes (Table 1), [19,21-23,25-29,31b,d,34-41] bioimaging (Table 2), [43][44][45][47][48][49][50][51][52][53][54] antimicrobial (Table 3), [57,[60][61][62][63][64][65][66][67] biosensing (Table 4), [69][70][71][72][73][75][76][77][78][79][80][81][82][83...…”

“…Another sustained-release therapeutic platform was reported by Sava Gallis et al on the basis of the encapsulation of antibacterial agent ceftazidime into ZIF-8 MOF for continuous treatment of intracellular infections. [57] Ceftazidime was successfully loaded into ZIF-8 through simple encapsulation strategy and demonstrated a long-term drug release up to 1 week. As a therapeutic platform, ceftazidime@ZIF-8 showed good biocompatibility on A549 cells and RAW 264.7 cells, and excellent antibacterial effect against E. coli.…”

Emerging nanobiomaterials against bacterial infections in postantibiotic era

“…Metal‐organic framework (MOF)‐based nanomaterials with outstanding (a) ability of loading various drugs, (b) biocompatibility and precise control of particle size, and (c) facile surface chemistry allowing conjugation of numerous functionalities show good potential to deliver the antibiotic intracellularly, which is a promising methodology to enhance the treatment of intracellular infections. McBride et al proposed a MOF‐based system as a valid slow‐release therapeutic carrier for treating intracellular infections 101 . The ceftazidime was encapsulated in ZIF‐8 nanoparticles as a potential therapeutic agent.…”

The Antibacterial Mechanism of Zn(II) Frame Supported on Alginate Membrane

“…This transporter plays an important role in the tricarboxylic acid cycle and will affect bacterial respiratory metabolism after being affected. 34 ZIF-8 not only releases metal ions, ligand 2-MI also has some antibacterial pro-perties. 35 In the current study, changes in cell membrane permeability, respiratory metabolism, cell morphology, and intracellular protein synthesis of E. coli were mainly studied.…”