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

Abstract

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 nanoparticlehydrogel (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 H 2 O 2 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.

pH-Responsive wound dressings: advances and prospects

“…Depending on composition, hydrogels are able to change their morphology, swelling behavior, degradation, or drug delivery efficiency based on the variation in pH; therefore, the wound healing process could be better regulated. 26,45,60 In this section, we discuss recent advances in pH-responsive hydrogel wound dressings from the perspective of function.…”

“…6(b)). 60 The denaturation of enzymes in bacteria is observed at temperatures above 50 1C, where the proteins and lipids of cell membranes are also damaged, causing bacterial death. Therefore, photothermal therapy has recently emerged as a means of combating bacteria.…”

Recent advances in responsive antibacterial materials: design and application scenarios

“…For example, Zu et al incorporated copper peroxide (CuO 2 ) nanoparticles into hydrogels to achieve a synergistic enhanced Fenton reaction. 52 The H + in the infection site could react with CuO 2 and generate Cu 2+ and H 2 O 2 . Subsequently, Cu 2+ was reduced by glutathione (GSH) to Cu + , which could catalyze the self-supplied H 2 O 2 to form highly toxic hydroxyl radical ( • OH).…”

“…[197][198][199] The dressings carrying endogenous or exogenous stimuli-responsive antibacterial materials have been widely studied to prevent AMR and promote wound healing. 43,52,[88][89][90]97,104,113,115,117,142,144,145,174,176 In this section, we mainly discuss the activatable antibacterial wound dressings for specific applications, including chronic, movable parts, post-operation, and burn wound healing.…”

Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

“…Te metal-ion component of metal peroxides takes part in a variety of biological processes, such as biochemical reactions and the process of tissue regeneration [42,43]. On this basis, metal peroxide-based nanoparticles serve as nascent nanosystem with distinct intrinsic physicochemical characteristics, reactive aspects, and bioactivities for fulflling diverse requirements of biological applications.…”