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

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.