Tear glucose-responsive and photo-activated antibacterial hydrogel bandage with bio-heterojunction for the treatment of drug-resistant bacterial corneal infection.

Abstract

Bacterial keratitis (BK) contributes to more than half of the cases of corneal infection, which is caused by bacterial infection on cornea. BK can lead to severe vision loss or even blindness if appropriate treatment is not provided in a timely manner. However, the indiscriminate use of antibiotics can lead to antimicrobial resistance and potential cytotoxicity to the surrounding healthy tissue. To provide effective and safe treatment for BK, an antibiotic-free tear glucose responsive and photoactive hydrogel bandage (tgr-PAHB) is established. The tgr-PAHB consists of poly-ε-lysine (pεK) hydrogel encapsulating photoactive graphene oxide/copper ferrite nanoparticles (GO/CFN) bio-heterojunction and immobilized tear-responsive glucose oxidase (GOx). GO/CFN rapidly eliminates bacteria by producing abundant reactive oxygen species (ROS) under near-infrared light (NIR) irradiation and catalyzing the GOx-produced hydrogen peroxide (H₂O₂). The strong antibacterial property of tgr-PAHB against Staphylococcus aureus and Pseudomonas aeruginosa were investigated in-vitro. Furthermore, the tgr-PAHB can eradicate drug-resistant S. aureus and P. aeruginosa on ex-vivo cornea efficiently. The tgr-PAHB also exhibits efficient treatment efficacy in drug-resistant P. aeruginosa-induced BK in rabbit models. This study suggests tgr-PAHB is promising for rapid and effective treatment for BK caused by antibiotic-resistant bacteria and elucidates a direction for antibiotic-free therapy against infective keratitis. STATEMENT OF SIGNIFICANCE: Bacterial keratitis (BK) is a major cause of irreversible corneal damage and blindness. The widespread use of antibiotics as first-line therapy contributes to increasing antimicrobial resistance, highlighting the need for alternative treatments. Non-antibiotic clinically applied strategies, such as riboflavin-based photodynamic therapy, are limited by risks of photodamage and unintended corneal collagen crosslinking. This article introduces a new reactive oxygen species (ROS)-based material, the Tear Glucose Responsive and Photo-Activated Antibacterial Hydrogel bandage (tgr-PAHB), for treating BK with a safer light source and reduced corneal penetration. The antibacterial efficacy of tgr-PAHB is demonstrated against both Gram-positive and Gram-negative bacteria with drug-resistance in ex-vivo porcine cornea and in-vivo rabbit models, suggesting its potential for broad applications in ocular and other tissue infections.