Synergistic Chemotherapy and Photodynamic Therapy of Endophthalmitis Mediated by Zeolitic Imidazolate Framework-Based Drug Delivery Systems

Small. 2019 Nov;15(47):e1903880. doi: 10.1002/smll.201903880. Epub 2019 Oct 7.

Abstract

Endophthalmitis, derived from the infections of pathogens, is a common complication during the use of ophthalmology-related biomaterials and after ophthalmic surgery. Herein, aiming at efficient photodynamic therapy (PDT) of bacterial infections and biofilm eradication of endophthalmitis, a pH-responsive zeolitic imidazolate framework-8-polyacrylic acid (ZIF-8-PAA) material is constructed for bacterial infection-targeted delivery of ammonium methylbenzene blue (MB), a broad-spectrum photosensitizer antibacterial agent. Polyacrylic acid (PAA) is incorporated into the system to achieve higher pH responsiveness and better drug loading capacity. MB-loaded ZIF-8-PAA nanoparticles are modified with AgNO3 /dopamine for in situ reduction of AgNO3 to silver nanoparticles (AgNPs), followed by a secondary modification with vancomycin/NH2 -polyethylene glycol (Van/NH2 -PEG), leading to the formation of a composite nanomaterial, ZIF-8-PAA-MB@AgNPs@Van-PEG. Dynamic light scattering, transmission electron microscopy, and UV-vis spectral analysis are used to explore the nanoparticles synthesis, drug loading and release, and related material properties. In terms of biological performance, in vitro antibacterial studies against three kinds of bacteria, i.e., Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus, suggest an obvious superiority of PDT/AgNPs to any single strategy. Both in vitro retinal pigment epithelium cellular biocompatibility experiments and in vivo mice endophthalmitis models verify the biocompatibility and antibacterial function of the composite nanomaterials.

Keywords: antibacterial materials; biofilms; endophthalmitis; metal-organic frameworks; photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemical synthesis
  • Acrylic Resins / chemistry
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Cell Survival / drug effects
  • Drug Delivery Systems*
  • Endophthalmitis / drug therapy*
  • Escherichia coli / drug effects
  • Escherichia coli / ultrastructure
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry*
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / ultrastructure
  • Metal-Organic Frameworks / chemistry
  • Mice
  • Microbial Sensitivity Tests
  • Particle Size
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology
  • Polyethylene Glycols / chemistry
  • Rabbits
  • Reactive Oxygen Species / metabolism
  • Retinal Pigment Epithelium / cytology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / ultrastructure
  • Surface Properties
  • Vancomycin / pharmacology
  • Zeolites / chemical synthesis
  • Zeolites / chemistry*

Substances

  • Acrylic Resins
  • Anti-Bacterial Agents
  • Imidazoles
  • Metal-Organic Frameworks
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • acidified zeolitic imidazolate framework-8
  • Zeolites
  • Polyethylene Glycols
  • carbopol 940
  • Vancomycin
  • imidazole