Zwitterionic chitosan-modified amorphous ZnCuAl-LDH eye drops for efficient treatment of bacterial keratitis

Bacterial keratitis caused by microbial invasion represents a significant cause of visual impairment characterized by corneal perforation, epithelial defect, intense pain, and conjunctival congestion. The widespread misuse of antibiotic eye drops in clinical treatment has accelerated the global rise of antibiotic-resistant infections, dimming the prospects for antibiotic therapy. In response, inorganic nanomaterial-based antibacterial eye drops have been developed for bacterial keratitis leveraging their structural controllability, composition diversity and ease of functionalization, However, they typically exert antibacterial effects with the assistance of laser, ultrasound, or X-ray irradiation that may cause irritation or damage to the human eye, or involve intricate structural modifications for antibacterial activation. Herein, we propose zwitterionic chitosan-modified defective amorphous ZnCuAl-layered double hydroxide nanosheets (ZC@a-LDH) as an antibacterial agent for bacterial keratitis treatment. ZC@a-LDH nanosheets demonstrate significantly enhanced antimicrobial efficacy compared with their defect-free counterparts, effectively suppressing bacterial proliferation at a minimum inhibitory concentration of 12 μg mL^-1 without relying on external stimuli. The enhanced antimicrobial performance may be attributed to the combined action of electrostatic interactions, antibacterial ions (Zn²⁺/Cu²⁺) and enhanced charge transport facilitated by structural defects. Notably, ZC@a-LDH antibacterial eye drops demonstrate effective intervention in bacterial keratitis in mice, outperforming the conventional tobramycin in therapeutic efficacy.