A Triple-Modal "One-Stone-for-Three-Birds" Strategy: Breaking Ocular Barriers to Combat Bacterial Keratitis With Antibacterial, Antioxidant and Anti-Inflammatory.

In the clinical management of bacterial keratitis, antimicrobial delivery is limited by short ocular surface retention and low bioavailability. Meanwhile, free radical damage and severe inflammation caused by bacterial invasion remain key clinical challenges. To address these issues, we developed a novel metal-phenolic nanoparticles (FCTP), which were self-assembled from ferric ions (Fe3 +), curcumin, tannic acid, and ε-poly-L-lysine through metal-phenolic networks and electrostatic interactions, and were loaded onto a dissolvable microneedle (MN) system for the treatment of bacterial keratitis. In vitro assays demonstrated that the obtained FCTP nanoparticles exhibited a potent and rapid bactericidal activity by disrupting the bacterial biofilm. They can also scavenge excessive free radicals in the corneal cells. Moreover, FCTP nanoparticles regulated macrophage polarization from M1 to M2 by modulating phosphorylation of NF-κB pathway kinases, significantly inhibiting pro-inflammatory cytokines (IL-6, TNF-α) and upregulating anti-inflammatory IL-10. In Vivo experiments verified that FCTP-loaded dissolvable MNs penetrated the corneal barrier and biofilm. Compared with eye drops, the MN showed superior efficacy in eradicating bacteria, relieving ocular inflammation, and promoting corneal epithelialization with a single administration. Overall, this multifunctional nanoplatform provides a promising strategy for ocular diseases by targeting infection, oxidative stress, inflammation, and physiological barriers.