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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 ?-lactamase Escherichia coli both in vitro and in vivo. Meanwhile, the released Cu²⁺ 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.

SUBMITTER: Qiao Y

PROVIDER: S-EPMC6727190 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Qiao Yue Y Ping Yuan Y Zhang Hongbo H Zhou Bo B Liu Fengyong F Yu Yinhui Y Xie Tingting T Li Wanli W Zhong Danni D Zhang Yuezhou Y Yao Ke K Santos Hélder A HA Zhou Min M

ACS applied materials & interfaces 20190115 4

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 c ...[more]

PMID: 30605311

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Project description:BackgroundCalophyllum inophyllum L. (Calophyllaceae) is an evergreen tree ethno-medically used along the seashores and islands of the Indian and Pacific Oceans, especially in Polynesia. Oil extracted from the seeds is traditionally used topically to treat a wide range of skin injuries from burn, scar and infected wounds to skin diseases such as dermatosis, urticaria and eczema. However, very few scientific studies reported and quantified the therapeutic properties of Calophyllum inophyllum oil (CIO). In this work, five CIO from Indonesia (CIO1), Tahiti (CIO2, 3), Fiji islands (CIO4) and New Caledonia (CIO5) were studied and their cytotoxic, wound healing, and antibacterial properties were presented in order to provide a scientific support to their traditional use and verify their safety.MethodsThe safety of the five CIO was ascertained using the Alamar blue assay on human keratinocyte cells. CIO wound healing properties were determined using the scratch test assay on human keratinocyte cells. CIO-stimulated antibacterial innate immune response was evaluated using ELISA by measuring β defensin-2 release in human derivative macrophage cells. CIO antibacterial activity was tested using oilogramme against twenty aerobic Gram- bacteria species, twenty aerobic Gram+ bacteria species, including a multi-drug resistant Staphylococcus aureus strain and two anaerobic Gram+ bacteria species e.g. Propionibacterium acnes and Propionibacterium granulosum. To detect polarity profile of the components responsible of the antibacterial activity, we performed bioautography against a Staphylococcus aureus strain.ResultsBased on Alamar Blue assay, we showed that CIO can be safely used on keratinocyte cells between 2.7% and 11.2% depending on CIO origin. Concerning the healing activity, all the CIO tested accelerated in vitro wound closure, the healing factor being 1.3 to 2.1 higher compared to control when keratinocytes were incubated after scratch with CIO at 0.1%. Furthermore, our results showed that CIO exhibit two distinct antibacterial effects: one against Gram+ bacteria by direct inhibition of mitotic growth and another potent effect against Gram- bacteria due to increased release of β-defensin 2 peptide by macrophages. Interestingly, the needed concentrations of CIO to inhibit bacteria growth and to promote wound healing are lower than concentrations exhibiting cytotoxic effects on keratinocyte cells. Finally, we performed bioautography assay against Staphylococcus aureus to determine polarity profile of the components responsible for CIO antibacterial activity. Our results showed for the five tested CIO that components responsible of the bacterial growth inhibition are the more polar one on the TLC chromatographic profile and are contained in the resinous fraction of the oil.ConclusionsThis study was conducted to evaluate cytotoxicity, wound healing and antibacterial properties of five CIO traditionally used to treat infected wounds. Using cell and bacteria cultures, we confirmed the pharmacological effects of CIO as wound healing and antimicrobial agent. Moreover, we showed that concentration of CIO needed to exhibit therapeutic effects are lower than concentrations exhibiting cytotoxic effects in vitro. For the first time, this study provides support for traditional uses of CIO. These wound healing and antibiotic properties make CIO a valuable candidate to treat infected wounds especially in tropical areas.

Dataset Information

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

Publications

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

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