Metal valence transition strategy-engineered bimetallic nanozyme thermosensitive hydrogel for deep-tissue therapy of subcutaneous abscess wounds and bacterial corneal ulcers.

Bacterial corneal ulcers pose considerable clinical challenges owing to their potential to induce vision impairment and even permanent blindness. Conventional antimicrobial eye drops are often limited by low corneal penetration and rising drug resistance. Herein, we developed a thermosensitive, soft ocular hydrogel integrated with metal valence transition strategy-engineered Fe-Co@D-Arg@PDA nanoparticles (FDP NPs) that enables antibacterial agent release in response to body temperature (37 °C) for the effective treatment of bacterial corneal ulcers. Upon 808-nm laser irradiation, the hydrogel initiates a synergistic therapeutic effect of photothermal and nitric oxide gas treatments, thereby enhancing the Fenton-like effect and remarkably improving the overall therapeutic efficacy for deep-tissue lesions. Density functional theory analysis indicates that FDP NPs transfer electrons via cobalt valence-state transitions to generate reactive oxygen species. Transcriptomic sequencing further revealed that bacteria treated with FDP NPs showed downregulation of gene expression of key enzymes involved in energy metabolism-related pathways. In vivo model experiments demonstrated that the wound healing rates for bacterial corneal ulcers and subcutaneous abscesses reached 95 % ± 5 % and 94 % ± 1 %, respectively. This study proposes a novel strategy for the treatment of severe ocular infections, aiming to offer a new approach to address the inherent drawbacks of ophthalmic medications.