International Journal of Nanomedicine (Mar 2024)
Bacteria-Targeting Nanoparticles with ROS-Responsive Antibiotic Release to Eradicate Biofilms and Drug-Resistant Bacteria in Endophthalmitis
Abstract
Jian Yu,1,2,* Huan Xu,1,2,* Jiaojiao Wei,1,2 Liangliang Niu,1,2 Haohao Zhu,1,3 Chunhui Jiang1,2 1Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Myopia of State Health Ministry and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, People’s Republic of China; 3Department of Ophthalmology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunhui Jiang, Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email [email protected] Haohao Zhu, Department of Ophthalmology, Shanghai Fifth People’s Hospital, Fudan University, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +86-21-64308151, Fax +86-21-64300477, Email [email protected]: Bacterial endophthalmitis is an acute progressive visual threatening disease and one of the most important causes of blindness worldwide. Current treatments are unsatisfactory due to the emergence of drug-resistant bacteria and the formation of biofilm.Purpose: The aim of our research was to construct a novel nano-delivery system with better antimicrobial and antibiofilm effects.Methods: This study developed a novel antibiotic nanoparticle delivery system (MXF@UiO-UBI-PEGTK), which is composed of (i) moxifloxacin (MXF)-loaded UiO-66 nanoparticle as the core, (ii) bacteria-targeting peptide ubiquicidin (UBI29-41) immobilized on UiO-66, and (iii) ROS-responsive poly (ethylene glycol)-thioketal (PEG-TK) as the surface shell. Then the important properties of the newly developed delivery system, including biocompatibility, toxicity, release percentage, thermal stability, ability of targeting bacteria, and synergistic antibacterial effects on bacterial biofilms and endophthalmitis, were evaluated.Results: In vitro, MXF@UiO-UBI-PEGTK exhibited significant antibiotic effects including the excellent antibiofilm property against Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus at high levels of ROS. Moreover, MXF@UiO-UBI-PEGTK demonstrated outstanding efficacy in treating bacterial endophthalmitis in vivo.Conclusion: This novel nanoparticle delivery system with ROS-responsive and bacteria-targeted properties promotes the precise and effective release of drugs and has significant potential for clinical application of treating bacterial endophthalmitis. Keywords: endophthalmitis, nanoparticles, bacterial biofilms, ROS-responsive, moxifloxacin
