Copper selenide nanosheets with photothermal therapy-related properties and multienzyme activity for highly effective eradication of drug resistance.

Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds.

pH-responsive double-enzyme active metal-organic framework for promoting the healing of infected wounds.

The abuse of antibiotics accelerates the spread and evolution of drug-resistant bacteria, which seriously threatens human health. Hydroxyl radicals (•OH) are generated by peroxidase in the presence of H2O2, which is strongly oxidizing and can effectively kill bacteria. However, high production costs and poor stability limit the clinical use of natural enzymes. "Nanozyme" is a general term for nanomaterials with catalytic activity similar to that of biological enzymes. Compared to biological enzymes, nanozymes have the advantages of low cost, facile preparation, and easy storage, making them a good choice for the development of antibacterial agents. Here, a nickel-based metal-organic framework (Ni-MOF) with dual enzymatic activity that switches depending on the pH environment was studied. In a slightly acidic environment, Ni-MOF can react with hydrogen peroxide to produce hydroxyl radicals that kill bacteria; in a neutral environment, Ni-MOF instead removes excessive reactive oxygen species (ROS) and promotes the transformation of macrophages into M2 macrophages. Compared to most nanozymes, Ni-MOF has unique electrical conductivity and better biosafety. The results of animal experiments show that Ni-MOF can not only treat infected wounds but also promote the healing of acute wounds and exhibits great clinical application potential.

Two-dimensional TiO nanosheets with photothermal effects for wound sterilization.

To combat multidrug-resistant bacteria, researchers have poured into the development and design of antimicrobial agents. Here, low-cost two-dimensional (2D) antibacterial material titanium monoxide nanosheets (TiO NSs) were prepared by an ultrasonic-assisted liquid-phase exfoliation method. When cultured with bacteria, TiO NSs showed intrinsic antimicrobial capacity, possibly due to membrane damage caused by the sharp edges of TiO NSs. Under near-infrared (NIR) laser irradiation, TiO NSs showed high photothermal conversion efficiency (PTCE) and sterilization efficiency. By combining these two antibacterial mechanisms, TiO NSs exhibited a strong killing effect on Gram-negative Escherichia coli (E. coli) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Especially after treatment with TiO NSs (150 µg mL-1) +near-infrared (NIR) light irradiation, both bacteria were completely killed. In vivo experiments on wound repair of bacterial infection further confirmed its antibacterial effect. In addition, TiO NSs had no obvious toxicity or side effects, so as a kind of broad-spectrum 2D antibacterial nanoagent, TiO NSs have broad application prospects in the field of pathogen infection.

Clinical application of polylactic acid/gelatin nanofibre membrane in hard-to-heal lower extremity venous ulcers.

OBJECTIVE: To evaluate the safety and effectiveness of polylactic acid/gelatin nanofibre membranes (PGNMs) in treating hard-to-heal lower extremity venous ulcer wounds. METHOD: In this prospective study, patients with venous leg ulcers (VLUs) were treated with PGNMs or standard of care. Wounds were assessed once a week until the wound was fully healed. RESULTS: The treatment group was comprised of 10 patients with VLUs, aged between 47-64 years, with an average age of 56.58±6.19 years. The wounds were located in the lower leg and/or ankle. Average wound area was 8.91±13.57cm2 (range: 1.5-52.5cm2). Average wound healing time was 18.75±16.36 days. Of the patients, nine (90%) rated their pain as lighter when removing the dressing, with an average pain value of 2.0±1.0 points. There was less secondary trauma to the wound surface, and less bleeding. At six months after the wound healing, the scar evaluation (using the Vancouver Scar Scale) result was 3.75±1.96 points. CONCLUSION: In this study, the PGNMs were safe and effective in treating hard-to-heal lower extremity VLUs.

Circular RNA hsa_circ_0000915 promotes propranolol resistance of hemangioma stem cells in infantile haemangiomas.

BACKGROUND: Propranolol is a first-line clinical drug for infantile haemangiomas (IH) therapy. Nevertheless, resistance to propranolol is observed in some patients with IH. Circular RNAs (circRNAs) has been increasingly reported to act as a pivotal regulator in tumor progression. However, the underlying mechanism of circRNAs in IH remains unclear. METHODS: Quantitative real-time polymerase chain reaction was performed to detect Circ_0000915, miR-890 and RNF187 expression. Protein levels were determined using western blot. CCK-8 assay was used to measure cell proliferation. Caspase-3 activity assay and flow cytometry were conducted to determine cell apoptosis. Luciferase reporter assay was carried out to assess the interaction between miR-890 and Circ_0000915 or RNF187. Chromatin immunoprecipitation assay was performed to detect the interaction between STAT3 and Circ_0000915 promoter. Biotin pull-down assay was used to detect the direct interaction between miR-890 and Circ_0000915. In vivo experiments were performed to measure tumor formation. RESULTS: Here, we discovered depletion of Circ_0000915 increased propranolol sensitivity of haemangioma derived stem cells (HemSCs) both in vitro and in vivo, whereas forced expression of Circ_0000915 exhibited opposite effects. Mechanistically, Circ_0000915, transcriptionally induced by IL-6/STAT3 pathway, competed with RNF187 for the biding site in miR-890, led to upregulation of RNF187 by acting as a miR-890 "sponge". Furthermore, silence of miR-890 reversed increased propranolol sensitivity of HemSCs due to Circ_0000915 ablation. Moreover, increased Circ_0000915 and RNF187 levels were observed in IH tissues and positively associated with propranolol resistance, miR-890 exhibited an inverse expression pattern. CONCLUSION: We thereby uncover the activation of IL-6/STAT3/Circ_0000915/miR-890/RNF187 axis in propranolol resistance of IH, and provide therapeutic implications for patients of IH with propranolol resistance.

Liquid exfoliation of V8C7 nanodots as peroxidase-like nanozymes for photothermal-catalytic synergistic antibacterial treatment.

Nanozymes are effective antibiotics that use reactive oxygen species (ROS) produced by Fenton/Fenton-like reactions to kill bacteria. However, its activity is still not satisfactory and requires large amounts of hydrogen peroxide (H2O2) with side effects on normal tissues. Herein, ultrasmall V8C7 nanodots (NDs) are successfully constructed by the liquid-phase exfoliation method for photothermal-catalytic synergistic antibacterial treatment. The prepared V8C7 NDs are horseradish peroxidase (HRP)-like nanozymes that can efficiently catalyze H2O2 to produce a large amount of ROS. Unlike traditional HRP-like nanozymes, V8C7 NDs can have a good catalytic effect under slightly acidic conditions (pH=5.5). Moreover, V8C7 NDs have good near-infrared (NIR) absorption and high photothermal conversion efficiency (PTCE, 50.39%), which can be used for photothermal treatment (PTT) of bacteria. In addition, the mild photothermal effect can further enhance the HRP-like catalytic activity of V8C7 NDs, thereby further enhancing the antibacterial performance of V8C7 NDs. In vitro results show that V8C7 NDs can effectively eradicate Escherichia coli (E. coli, gram-negative) and methicillin-resistant Staphylococcus aureus (MRSA, gram-positive) under laser irradiation and the presence of H2O2, possessing spectral antibacterial properties. More importantly, V8C7 NDs display satisfactory therapeutic effects on wounds infected by MRSA in vivo, and their toxicity is negligible, suggesting that they may have great potential for application as powerful and safe antibacterial agents. This work presents a practical antibacterial strategy by combining PTT and catalytic therapy to achieve efficient treatment of bacteria-infected wounds. STATEMENT OF SIGNIFICANCE: (1) Ultrasmall V8C7 NDs were prepared by the liquid-phase exfoliation method. (2) V8C7 NDs showed good photothermal, catalytic properties. (3) V8C7 NDs achieved satisfactory photothermal-catalytic synergistic antibacterial treatment.

Instant in-situ Tissue Repair by Biodegradable PLA/Gelatin Nanofibrous Membrane Using a 3D Printed Handheld Electrospinning Device.

Background: This study aims to design a 3D printed handheld electrospinning device and evaluate its effect on the rapid repair of mouse skin wounds. Methods: The device was developed by Solidworks and printed by Object 350 photosensitive resin printer. The polylactic acid (PLA)/gelatin blend was used as the raw material to fabricate in-situ degradable nanofiber scaffolds. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and water vapor permeability test were used to evaluate the material properties of the scaffolds; cytotoxicity test was performed to evaluate material/residual solvent toxicity, and in situ tissue repair experiments in Balb/c mouse were performed. Results: The 3D printed handheld electrospinning device successfully fabricates PLA/gelatin nanofibrous membrane with uniformly layered nanofibers and good biocompatibility. Animal experiments showed that the mice in the experimental group had complete skin repair. Conclusions: The 3D printed handheld device can achieve in situ repair of full-thickness defects in mouse skin.