1. Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
2. Institute of Translational Medicine, Zhejiang University, Hangzhou, 310009, China.
3. Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, 310009, China.
4. Department of Pharmaceutical Science, Åbo Akademi University; Turku Bioscience Center, University of Turku and Åbo Akademi University, FI-20520, Finland.
5. Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Finland.
6. Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Zhejiang University, Hangzhou, 310009, China.
7. State Key Laboratory of Modern Optical Instrumentations, Zhejiang University, Hangzhou, 310058, China.
8. Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland.
9. Helsinki Institute of Life Science (HiLIFE), University of Helsinki, FI-00014 Helsinki, Finland.
* Equal contribution
Rationale: Endophthalmitis, which is one of the severest complications of cataract surgeries, can seriously threaten vision and even lead to irreversible blindness owing to its complicated microenvironment, including both local bacterial infection and severe inflammation. It is urgent to develop a comprehensive treatment for both anti-bacterial and anti-inflammatory effects.
Methods: Herein, we developed AuAgCu2O-bromfenac sodium nanoparticles (AuAgCu2O-BS NPs), which was designed to combine anti-bacterial and anti-inflammatory effects for integrated therapy of endophthalmitis after cataract surgery. The AuAgCu2O-BS NPs could eradicate methicillin-resistant Staphylococcus aureus (MRSA) bacterial strain relied on their photodynamic effects and the release of metal ions (Ag+ and Cu+) by the hollow AuAgCu2O nanostructures mediated mild photothermal effects. The anti-inflammatory drug, bromfenac sodium, released from the nanoparticles were able to significantly reduce the local inflammation of the endophthalmitis and promote tissue rehabilitation. In vivo bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model.
Results: Excellent antibacterial ability of AuAgCu2O-BS NPs was verified both in vitro and in vivo. Ophthalmological clinical observation and pathologic histology analysis showed prominent treatment of inflammatory reaction. Importantly, the mild temperature photothermal effect not only promoted the release of metal ions and bromfenac sodium but also avoided the thermal damage of the surrounding tissues, which was more suitable for the practical application of ophthalmology due to the complex structure of the eyeball. Moreover, superior biocompatibility was approved by the preliminary toxicity investigations, including low cytotoxicity, negligible damage to major organs, and stable intraocular pressure.
Conclusions: Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.
Keywords: endophthalmitis, antibacterial and anti-inflammation effect, mild photothermal therapy, nanoparticles, post-cataract Surgery