Gallium-Based Nanoplatform for Combating Multidrug-Resistant Pseudomonas aeruginosa and Postoperative Inflammation in Endophthalmitis Secondary to Cataract Surgery.

Abstract

Postcataract endophthalmitis (PCE), a devastating complication following cataract surgeries, is one of the most crucial diseases causing irreversible eye blindness. Pseudomonas aeruginosa (PA), a multiple-drug-resistance (MDR) pathogen, always leads to uncontrolled infection and severe inflammation in PCE that can be difficult to treat by antibiotics. Therefore, it is urgent to develop new feasible strategies composed of both antibacterial and anti-inflammatory capabilities. Here, we report a multifunctional non-antibiotic nanoplatform (Ga-mSiO2-BFN) comprised of clinically approved gallium, mesoporous silica, and bromfenac (BFN) as a co-modified release system to simultaneously eradicate MDR-PA infection and cure inflammation for PCE. The released gallium ions can disrupt bacterial iron metabolism. Meanwhile, the simultaneously released BFN can suppresses the inflammation both postoperation and postinfection of PCE. In the PCE rabbit model, the slit-lamp dispersion and retro-illumination micrograph, ophthalmic clinical grading, and etiological histopathology analysis demonstrated that Ga-mSiO2-BFN could eradicate the MDR infection and alleviate the secondary inflammation from MDR-PA infection. Moreover, both cellular biocompatibility and in vivo animal model application verified the biocompatibility. A potential antibacterial mechanism implicated in the antibacterial action was demonstrated by comprehensive assays of iron antagonism evolutionary curve, colony autofluorescence, polymerase chain reaction, and electron microscopy, showing a repressing siderophore peptide pyoverdine, pyoverdine synthetase D, and interfering with bacterial DNA synthesis. All composites of our nanoplatform were FDA approved, making the Ga-mSiO2-BFN as a potentially promising therapeutic approach for treating MDR-PA in PCE accompanying satisfactory prognosis and prospects for clinical translations.