ROS-scavenging glyco-nanoplatform for synergistic antibacterial and wound-healing therapy of bacterial keratitis

Abstract

Infectious keratitis is a serious disease originating when corneal trauma is infected with bacteria and has difficulties in healing due to stubborn infection and persistent inflammation featuring high reactive oxygen species (ROS) concentrations. Herein, a synergistic antibacterial and wound-healing strategy is proposed to treat bacterial keratitis by using poly(phenylboronic acid-(3,4-dihydropyrimidin-2(1H)-one))-co-(2-lactobionamidoethyl methacrylate) (p(PBA-DHPM-r-LAMA)) glycopolymeric micelles. The phenylboronic acid-(3,4-dihydropyrimidin-2(1H)-one) (PBA-DHPM) groups not only act as active targeting ligands to allow epithelial penetration and bacterial anchorage, but also perform as effective ROS-scavenging agents to relieve inflammation. By co-encapsulating levofloxacin (LEV) and chondroitin sulfate (CS) into the antioxidant glycopolymeric micelles, the resulting nanoplatform can achieve multiple functions of bacterial killing, ROS scavenging and promoting wound healing. Regarding the positive control, the nanoplatform demonstrated reasonable and comparable free radical scavenging potential in terms of DPPH, ABTS and hydroxyl radical scavenging. In addition, the glycopolymeric nanoplatform exhibited enhanced antibacterial activity compared to free LEV benefiting from the promoted epithelial penetration and the bacteria-activated drug release pattern. In vivo treatment of Staphylococcus aureus (S. aureus)-induced bacterial keratitis on a rat model showed that the drug-loaded nanoplatform could effectively cure bacterial keratitis within 5 days. Overall, this work provides an effective antibacterial and wound-healing strategy based on a ROS-scavenging polymeric nanoplatform for treating bacterial keratitis.