Laser-Activatable CuS Nanodots to Treat Multidrug-Resistant Bacteria and Release Copper Ion to Accelerate Healing of Infected Chronic Nonhealing Wounds

Abstract

Chronic nonhealing wounds have imposed serious challenges in the clinical practice, especially for the patients infected with multidrug-resistant microbes. Herein, we developed an ultrasmall copper sulfide (covellite) nanodots (CuS NDs) based dual functional nanosystem to cure multidrug-resistant bacteria-infected chronic nonhealing wound. The nanosystem could eradicate multidrug-resistant bacteria and expedite wound healing simultaneously owing to the photothermal effect and remote control of copper-ion release. The antibacterial results indicated that the combination treatment of photothermal CuS NDs with photothermal effect initiated a strong antibacterial effect for drug-resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum β-lactamase Escherichia coli both in vitro and in vivo. Meanwhile, the released Cu 2+ could promote fibroblast cell migration and endothelial cell angiogenesis, thus accelerating wound-healing effects. In MRSA-infected diabetic mice model, the nanosystem exhibited synergistic wound healing effect of infectious wounds in vivo and demonstrated negligible toxicity and nonspecific damage to major organs. The combination of ultrasmall CuS NDs with photothermal therapy displayed enhanced therapeutic efficacy for chronic nonhealing wound in multidrug-resistant bacterial infections, which may represent a promising class of antibacterial strategy for clinical translation.

Functional Biomaterials for Treatment of Chronic Wound

“…As shown in Figure 1, the synergistic action of the photothermal effect of the CuS nanodots and the release of copper ions produced a robust bactericidal effect on ESBL E. coli and MRSA in vitro. Further in vivo experiments used an MRSA-infected circular wound with a diameter of 0.7 cm in diabetic mice, and found that the experimental group basically healed after 12 days (Qiao et al, 2019).…”

Using a visible light-triggered pH switch to activate nanozymes for antibacterial treatment

“…Importantly, these two capacities were both pH dependent and could be simultaneously activated by visible light in the presence of a photoacid. In previous reports, 19,26 CuS NPs exhibited signicant antibacterial activity due to their photothermal conversion performance. In our experiments, we demonstrated that CuS NPs could also showed the excellent antibacterial capability through exerting their enzyme mimicking activity.…”

Correlation between Elemental Composition/Mobility and Skin Cell Proliferation of Fibrous Nanoclay/Spring Water Hydrogels

“…This element has been demonstrated to increase the expression of TGF-β1 in ex vivo skin models, thus leading to higher pro-collagen 1 and elastin production by fibroblasts [ 67 ]. Moreover, Cu has been demonstrated to enhance skin cell migration (keratinocytes and fibroblasts), which is crucial for wound healing [ 68 , 69 ]. ALIPS9 and ALIG30@10 were shown to favor fibroblast migration in a previous study [ 17 ], which could be related to copper release.…”