Cascade-reaction chemistry can generate
reactive-oxygen-species that can be used for the eradication of infectious biofilms. However, suitable and sufficient
oxygen sources are not always available near an
infection site, while the
reactive-oxygen-species generated are short-lived. Therefore, we developed a magnetic cascade-reaction container composed of mesoporous Fe3O4@SiO2 nanoparticles containing
glucose-oxidase and
l-arginine for generation of
reactive-oxygen-species.
Glucose-oxidase was conjugated with APTES facilitating coupling to Fe3O4@SiO2 nanoparticles and generation of H2O2 from
glucose.
l-arginine was loaded into the nanoparticles to generate NO from the H2O2 generated. Using an externally-applied magnetic field, cascade-reaction containers could be homogeneously distributed across the depth of an infectious biofilm. Cascade-reaction containers with coupled
glucose-oxidase were effective in killing planktonic, Gram-positive and Gram-negative bacteria. Additional efficacy of the
l-arginine based second cascade-reaction was only observed when H2O2 as well as NO were generated in-biofilm. In vivo accumulation of cascade-reaction containers inside abdominal Staphylococcus aureus biofilms upon magnetic targeting was observed real-time in living mice through an implanted, intra-vital window. Moreover,
vancomycin-resistant, abdominal S. aureus biofilms could be eradicated consuming solely endogenous
glucose, without any
glucose addition. Herewith, a new, non-
antibiotic-based infection-control strategy has been provided, constituting a welcome addendum to the shrinking clinical armamentarium to control
antibiotic-resistant
bacterial infections.