A Copper Peroxide Fenton Nanoagent-Hydrogel as an In Situ pH-Responsive Wound Dressing for Effectively Trapping and Eliminating Bacteria

Bacterial infection has been a great threat to wounds due to the abuse of antibiotics and drug resistance. Elaborately constructing an efficient antibacterial strategy for accelerated healing of bacteria-infected wounds is of great importance. Herein, we develop a transferrin-conjugated copper peroxide nanoparticle-hydrogel (denoted as CP@Tf-hy) wound dressing with no toxicity to mammalian cells at a test dosage. When exposed to an initial acidic wound environment, the CP@Tf-hy simultaneously displays in situ self-supplied H2O2 and pH-responsive release of Fenton catalytic copper ions accompanied by highly toxic hydroxyl radical (•OH) generation against antibiotic-resistant bacteria. Meanwhile, the positively charged CP@Tf-hy can efficiently trap and restrain negatively charged bacteria to the range of •OH destruction to greatly overcome its intrinsic disadvantages of short life and diffusion distance. Importantly, the CP@Tf-hy consumes the bacterial overexpressed antioxidant glutathione while boosting Fenton catalytic copper(I) ions to generate more •OH. The synergistic effects of the enhanced Fenton reaction, responsive copper ion release, and bacterial trapping can achieve high bacterial elimination efficacy (7 log reduction). In vivo investigations demonstrate that the porous CP@Tf-hy significantly promotes hemostasis, cell proliferation, and migration of the wound, consequently accelerating bacteria-infected wound healing. The safe, low-cost, and all-in-one CP@Tf-hy holds great prospects as an antibacterial dressing for rapid resistant bacteria-infected purulent wound healing.