Magnetically retained and glucose-fueled hydroxyl radical nanogenerators for H2O2-self-supplying chemodynamic therapy of wound infections.

ABSTRACT

Chemodynamic therapy (CDT) involving the highly toxic hydroxyl radical (OH) has exhibited tremendous potentiality in combating bacterial infection. However, its antibacterial efficacy is still unsatisfactory due to the insufficient H2O2 levels and near neutral pH at infection site. Herein, a glucose-fueled and H2O2-self-supplying OH nanogenerator (pFe3O4@GOx) based on cascade catalytic reactions is developed by immobilizing glucose oxidase (GOx) on the surface of PAA-coated Fe3O4 (pFe3O4). Magnetic pFe3O4 can act as a horseradish peroxidase-like nanozyme, catalyzing the decomposition of H2O2 into OH under acidic conditions for CDT. The immobilized GOx can continuously convert non-toxic glucose into gluconic acid and H2O2, and the former improves the catalytic activity of pFe3O4 nanozymes by decreasing pH value. The self-supplying H2O2 molecules effectively enhance the OH generation, resulting in the high antibacterial efficacy. In vitro studies demonstrate that the pFe3O4@GOx conducts well in reducing pH value and improving H2O2 level for self-enhanced CDT. Moreover, the cascade catalytic reaction of pFe3O4 and GOx effectively avoids strong toxicity caused by directly adding high concentrations of H2O2 for CDT. It is worth mentioning that the pFe3O4@GOx performs highly efficient in vivo CDT of bacteria-infected wound via the localized long-term magnetic retention at infection site and causes minimal toxicity to normal tissues at therapeutic doses. Therefore, the developed glucose-fueled OH nanogenerators are a potential nano-antibacterial agent for the treatment of wound infections.