In a previous communication, we reported a new method of synthesis of stable metallic copper nanoparticles (Cu-NPs), which had high potency for bacterial cell filamentation and cell killing. The present study deals with the mechanism of filament formation and antibacterial roles of Cu-NPs in E. coli cells. Our results demonstrate that NP-mediated dissipation of cell membrane potential was the probable reason for the formation of cell filaments. On the other hand, Cu-NPs were found to cause multiple toxic effects such as generation of reactive oxygen species, lipid peroxidation, protein oxidation and DNA degradation in E. coli cells. In vitro interaction between plasmid pUC19 DNA and Cu-NPs showed that the degradation of DNA was highly inhibited in the presence of the divalent metal ion chelator EDTA, which indicated a positive role of Cu(2+) ions in the degradation process. Moreover, the fast destabilization, i.e. the reduction in size, of NPs in the presence of EDTA led us to propose that the nascent Cu ions liberated from the NP surface were responsible for higher reactivity of the Cu-NPs than the equivalent amount of its precursor CuCl2; the nascent ions were generated from the oxidation of metallic NPs when they were in the vicinity of agents, namely cells, biomolecules or medium components, to be reduced simultaneously.

https://iopscience.iop.org/article/10.1088/0957-4484/25/13/135101/pdf

Mechanism of antibacterial activity of copper nanoparticles.

Wound healing is an intricate process that requires complex coordination between many cells and an appropriate extracellular microenvironment Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia While there has been intense investigation to find new methods to improve cutaneous wound care; the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds including excessive inflammation, ischemia, scarring and wound infection This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or currently used in clinical practice

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Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing.

Chitosan Based Metallic Nanocomposite Scaffolds as Antimicrobial Wound Dressings

Chitosan-based copper nanocomposite accelerates healing in excision wound model in rats.

Mercaptocarboxylic acids with different carbon chain lengths were used for stabilizing uniform 15 nm copper nanoparticles. The effects of surface chemistry such as ligand type and surface oxidation on the reactive oxygen species (ROS) generated by the copper nanoparticles were examined. Transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), UV-vis spectroscopy, and an acellular ROS assay show that ROS generation is closely related to the surface oxidation of copper nanoparticles. It was found that the copper nanoparticles with longer chain ligands had surfaces that were better protected from oxidation and a corresponding lower ROS generating capacity than did particles with shorter chain ligands. Conversely, the copper nanoparticles with greater surface oxidation also had higher ROS generating capacity.

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Effects of surface chemistry on the generation of reactive oxygen species by copper nanoparticles.

Results of a study on the wound-healing potential and physicochemical characteristics of copper nanoparticles prepared by high-temperature condensation and modified with a variety of agents (including oxygen, water vapors, and air) are reported. The modification of copper nanoparticles under monitored conditions guarantees the synthesis of particle species differing in size, phase composition, thickness, and composition of the oxide layer. Modified copper nanoparticles in the form of an ointment showed wound-healing behavior that differs in effectiveness depending on their physicochemical parameters. Nanoparticles of copper oxide (sample 7) (modified with air), with a particle size of 119 nm and crystalline copper content of ∼0.5%, and copper nanoparticles (sample 2) (modified with oxygen), with a particle size of 103 nm and crystalline copper content of 96%, demonstrated the maximum specific rate of wound adhesion.

Wound-healing properties of copper nanoparticles as a function of physicochemical parameters

Data on the antimicrobial effect of copper nanoparticles with different sizes, phase compositions, and surface oxide film thicknesses are represented. The nanoparticles under study show an antibacterial effect against the cells of the test species, Gram positive (Staphylococcus albus) and Gram negative (Escherihia coli) strains. The differences in toxicity observed for nanoparticles with varying dispersions and phase compositions are related to both specific features of the microorganism strains and nanoparticle concentration and properties.

Antimicrobial effect of copper nanoparticles with differing dispersion and phase composition

The wound-healing properties of organic and inorganic nanoparticles, ie, chitosan and copper nanoparticles, cointroduced into an ointment preparation, were investigated When used individually in the ointment, copper oxide nanoparticles at a concentration of 0002% and a level of oxidation of up to 90% and nanoparticles of chitosan at a concentration of 0002% prepared from chitosan with a molecular weight of 10 kDa demonstrated the most profound wound-healing effect The simultaneous introduction of chitosan and copper nanoparticles into the ointment composition led to a synergistic effect The most pronounced wound healing was observed for complex ointment preparations containing Cu1Ox sample 2 copper nanoparticles at a concentration of 0002% and chitosan nanoparticles synthesized from low-molecularweight chitosan (Mw 10 kDa) with a degree of deacetylation (DD) of 89% at a concentration of 0002% An additive effect was observed for the complex ointment in comparison with ointment preparations based on individual components Similar antibacterial effects were observed in ointment preparations based on organic and inorganic nanoparticles

Concomitant action of organic and inorganic nanoparticles in wound healing and antibacterial resistance: Chitosan and copper nanoparticles in an ointment as an example

The results concerning changes in the ESR signal of hemoglobin nitrosyl complexes in wound tissues in the course of healing by the action of ointments with copper nanoparticles (patent N2460532, Russia) are presented. It is shown that the wound healing process modified by the influence of copper nanoparticles demonstrates the increase in the ESR signal amplitude for hemoglobin nitrosyl complexes as compared with controls (the ointment base without nanoparticles). Planimetric measurements of wound area through reparation course indicate an active process of wound healing for injuries treated with copper nanoparticles in the ointment, resulting in lessening half-reparation time up to 5.0 times as compared with controls (treatment with the ointment base). The paper discusses the role of copper nanoparticles, NO and their potential synergistic effect on the skin wound regeneration.

A. A. Rakhmetova

Papers

Wound-healing properties of copper nanoparticles as a function of physicochemical parameters

Antimicrobial effect of copper nanoparticles with differing dispersion and phase composition

Concomitant action of organic and inorganic nanoparticles in wound healing and antibacterial resistance: Chitosan and copper nanoparticles in an ointment as an example

[Copper-induced change in the ESR signal of hemoglobin nitrosyl complexes in wound by the action of copper nanoparticles].