Light-Activatable Synergistic Therapy of Drug-Resistant Bacteria-Infected Cutaneous Chronic Wounds and Nonhealing Keratitis by Cupriferous Hollow Nanoshells

Abstract

Due to the inability to spontaneously heal and vulnerability to bacterial infection, diabetic patients are frustrated by unexpected epithelium injuries in daily life. Notably, a drug-resistant bacterial infection may result in a long-term impact to the natural function of damaged organs. It is imperative to develop strategies that promote injury recovery and eradicate drug-resistant infection simultaneously. Here, we present a composite structured cupriferous hollow nanoshell (AuAgCu₂O NS) that consists of a hollow gold-silver (AuAg) core and Cu₂O shell as a photothermal therapeutic agent for a cutaneous chronic wound and nonhealing keratitis with drug-resistant bacterial infection. The controllable photothermal therapeutic effect and released silver ion from the hollow AuAg core possess a synergistic effect to eradicate multi-drug-resistant bacteria, including extended-spectrum β-lactamase <i>Escherichia coli</i> (ESBL <i>E. coli</i>) and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Meanwhile, the released copper ion from the Cu₂O shell could expedite endothelial cell angiogenesis and fibroblast cell migration, thus boosting wound-healing effects. In both infection-complicated disease models, the ophthalmic clinical score, wound closure rates, and histopathology analysis demonstrate that the AuAgCu₂O NSs could facilitate the re-epithelialization at the wound area and eliminate the complicated bacterial infection from diabetic mice. A primary signal path involved in the promoted healing effect was further illustrated by comprehensive assays of immunohistochemical evaluation, Western blot, and quantitative polymerase chain reaction. Taken together, our AuAgCu₂O NSs are shown to be potent candidates for clinical utilization in the treatment of diabetic epithelium injuries.