Biomineralization nanozyme-based biodegradable microneedle for accelerating bacteria-infected diabetic wound healing

Drug-resistant bacterial infections in diabetic wound severely impair healing and may lead to life-threatening complications. Herein, a simple glucose oxidase (GOX) biomineralization nanozyme of GOX@CeO₂ was prepared which was further encapsulated with polydopamine (PDA) nanolayer (GOX@CeO₂@PDA termed as GCP_NPs) for diabetic wounds treatment. Due to the GOX and peroxidase (POD)-like activities of GCP_NPs, the excessive glucose at wound site could be consumed to conduct starvation therapy, which also activated cascade reaction to generate reactive oxygen species (ROS) to achieve chemodynamic therapy (CDT). The synergistic effect of cryogenic photothermal therapy (C-PTT) from PDA nanolayer could boost the wound healing. To further improve the therapy efficiency, biodegradable microneedles (MNs) were prepared to encapsulate the GCP_NPs, facilitating intimate contact between the nanodrugs and the deeper layers of the wound. In vitro and in vivo experimental results demonstrate the remarkable antibacterial property of the GCP_NPs against drug-resistant bacteria via the synergistic function of starvation therapy, CDT and C-PTT, which could promote epidermal tissue formation and collagen deposition to accelerate wound healing with negligible damage to healthy tissues. The consumption of glucose also contributes to the recovery of diabetic mice. These results highlight the potential of GCP_NPs in the treatment of bacterial infected diabetic wounds.