An Injectable Dual Bacterial-Trapping Nanozyme Composite Hydrogel for Synergistic Antibacterial/Anti-Inflammatory Therapy of Endophthalmitis

Abstract

Bacterial endophthalmitis (BE) is characterized by severe intraocular bacterial infection and sustained inflammation. Current therapeutic efficacy is compromised by the passive diffusion-dominated drug release kinetics of conventional carriers, leading to inadequate bacterial clearance and frequent invasive injections. Herein, an injectable hydrogel is engineered to achieve a synergistic “trap-and-kill” and immunomodulatory therapy. The hydrogel matrix is constructed via dynamic Schiff base crosslinking between quaternized chitosan and oxidized dextran, providing excellent injectability and biocompatibility. The hydrogel integrates boronic acid-decorated cerium metal-organic frameworks (Ce-MOFs) within this dynamic polysaccharide network, possessing dual bacterial-trapping attributed to boronic acid-mediated bacterial surface covalent binding to surface cis-diols and electrostatic attraction. This “bacterial enrichment” effect overcomes the diffusion barrier, markedly enhancing the bactericidal efficiency of the encapsulated vancomycin, resulting in a reduction in the dosage to as low as 14–20% of the clinical amount, yet the effect remains comparable. Furthermore, leveraging the catalase- and superoxide dismutase-mimicking activities of Ce-MOFs, the hydrogel functions as a therapeutic nanozyme to scavenge excessive reactive oxygen species (ROS) and downregulate pro-inflammatory cytokines. Validated by comprehensive in vitro and in vivo models, this integrated platform demonstrates superior bacterial eradication and inflammation resolution, which presents an active, robust therapeutic strategy for those deep-seated implant-associated infections.