Diabetic foot ulcers infected with
antibiotic-resistant bacteria form a severe complication of diabetes. Antimicrobial-loaded
hydrogels are used as a dressing for infected
wounds, but the ongoing rise in the number of antimicrobial-resistant
infections necessitates new, nonantibiotic based designs. Here, a
guanosine-quadruplex (G4 )-hydrogel composed of
guanosine,
2-formylphenylboronic acid, and
putrescine is designed and used as a cascade-reaction container. The G4 -
hydrogel is loaded with
glucose-oxidase and
hemin. The first cascade-reaction, initiated by
glucose-oxidase, transforms
glucose and O2 into
gluconic acid and H2 O2 . In vitro, this reaction is most influential on killing Staphylococcus aureus or Pseudomonas aeruginosa in
suspension, but showed limited killing of bacteria in biofilm-modes of growth. The second cascade-reaction, however, transforming H2 O2 into
reactive-oxygen-species (ROS), also enhances killing of biofilm bacteria due to
hemin penetration into biofilms and interaction with eDNA G-quadruplexes in the biofilm matrix. Therewith, the second cascade-reaction generates ROS close to the target bacteria, facilitating killing despite the short life-time of ROS. Healing of infected
wounds in diabetic mice proceeds faster upon coverage by these G4 -
hydrogels than by clinically common
ciprofloxacin irrigation. Moreover, local
glucose concentrations around infected
wounds decrease. Concluding, a G4 -
hydrogel loaded with
glucose-oxidase and
hemin is a good candidate for infected
wound dressings, particularly in diabetic patients.