A Guanosine‐Quadruplex Hydrogel as Cascade Reaction Container Consuming Endogenous Glucose for Infected Wound Treatment—A Study in Diabetic Mice

Abstract

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 H2O2. 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 H2O2 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.

Single Copper Atom Photocatalyst Powers an Integrated Catalytic Cascade for Drug-Resistant Bacteria Elimination

“…After separation and calcination, the G–metal powders were eventually prepared (Figure S1). In our previous research, we found that guanosine, with a ribose ring attached to G via a β- N 9 -glycosidic bond, could form much more stable G-quartet structures in an aqueous solution, − yielding hydrogels other than sediments. To simplify the fabrication process, we used G as a building block to construct our complexes in this study.…”

Nucleopeptide-Coupled Injectable Bioconjugated Guanosine-Quadruplex Hydrogel with Inherent Antibacterial Activity

“…Recently, a G-quadruplex hydrogel derived from the self-assembly of guanosine, 2-formylphenylboronic acid, and putrescine was used as a cascade reaction container to produce reactive oxygen species (ROS) from glucose. Furthermore, the multicomponent-derived self-assembled system was reported to have antibacterial activity with excellent in vivo diabetic wound care behavior . However, there are few reports wherein antibiotic-free G-quadruplex hydrogels have been shown to exhibit inherent antibacterial activity.…”

“…Furthermore, the multicomponent-derived self-assembled system was reported to have antibacterial activity with excellent in vivo diabetic wound care behavior. 38 However, there are few reports wherein antibiotic-free G-quadruplex hydrogels have been shown to exhibit inherent antibacterial activity. The incorporation of nucleobases into the peptide sequence results in the formation of different classes of biomaterials, named nucleopeptides (NPs), 39 and such NPs could be effectively used to form supramolecular hydrogels with potential applications.…”

Mimic enzymatic preparation of conductive supramolecular-polymeric hydrogels with antibacterial and antioxidant properties for accelerating wound healing

“…17 Recently, a naturally derived guanosine (G)-based supramolecular hydrogel (namely G4 hydrogel) was fabricated via the self-assembly of G and KB(OH) 4 , which involves cation-templated formation of G-quartet motifs and nanofibrils. 25,26 Hemin could be incorporated into G-quartet networks via co-assembly, obtaining an enzyme-like nanofibrous hydrogel (namely H/G4 hydrogel), and polyaniline was further introduced into a H/G4 scaffold by in situ catalytic deposition in order to prepare conductive hybrid hydrogels as biosensors. 27…”