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Synergistic Chemotherapy and Photodynamic Therapy of Endophthalmitis Mediated by Zeolitic Imidazolate Framework‐Based Drug Delivery Systems
Authors:Hao Chen  Jie Yang  Lin Sun  Hengrui Zhang  Yishun Guo  Jia Qu  Wenya Jiang  Wei Chen  Jian Ji  Ying‐Wei Yang  Bailiang Wang
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
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