Mild temperature photothermal assisted anti-bacterial and anti-inflammatory nanosystem for synergistic treatment of post-cataract surgery endophthalmitis

<b>Rationale:</b> 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. <b>Methods:</b> 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 <i>Staphylococcus aureus</i> (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. <i>In vivo</i> bacterial elimination and anti-inflammation were confirmed by a postcataract endophthalmitis rabbit model. <b>Results:</b> Excellent antibacterial ability of AuAgCu₂O-BS NPs was verified both <i>in vitro</i> and <i>in vivo</i>. 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. <b>Conclusions:</b> Our studies of nanosystem provide a promising synergic therapeutic strategy for postcataract endophthalmitis treatment with favorable prognosis and promise in clinical translations.