Carbonized nanogels for simultaneous antibacterial and antioxidant treatment of bacterial keratitis

Abstract

To prevent visual loss, clinical therapy of severe bacterial keratitis (BK) demands simultaneous remedying of the damage caused by bacterial infection and its induced oxidative stress/inflammation of the cornea. Here, we have developed a one-step method to synthesize carbonized nanogels (CNGs) from biogenic quercetin (Qu) and lysine (Lys) as a bifunctional agent with antibacterial and antioxidant properties for topical BK therapy. These Qu/Lys-CNGs synthesized by dry heating inherit and amplify the advantages of two natural products, including excellent antioxidant capacity and high positive charge. The Qu/Lys-CNGs display broad-spectrum bacteriostatic effects against non-multidrug-resistant bacteria, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella enteritidis, and also against multidrug-resistant bacteria, methicillin-resistant Staphylococcus aureus. Disintegration of peripheral structures of the bacteria caused by Qu/Lys-CNGs is due to their strong and specific interaction with bacterial membranes. In vitro cytotoxicity and hemolysis assays and in vivo corneal biocompatibility evaluations revealed good biocompatibility of Qu/Lys-CNGs as a safe nanomedicine in ophthalmic drop formulation. Furthermore, the Qu/Lys-CNGs can penetrate into the cornea via epithelial tight junction opening, thereby exerting superior antibacterial and antioxidant therapeutic effects against S. aureus-induced keratitis in rabbits. Our results indicate Qu/Lys-CNGs could be an effective bifunctional agent for clinical applications to treat bacterial ocular diseases.