Antibacterial activity of zinc oxide nanoparticles (ZnO-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. ZnO-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. ZnO is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered ZnO-NPs antibacterial activity including testing methods, impact of UV illumination, ZnO particle properties (size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory concentration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), OH− (hydroxyl radicals), and O2 −2 (peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to ZnO-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions. These have led to mitochondria weakness, intracellular outflow, and release in gene expression of oxidative stress which caused eventual cell growth inhibition and cell death. In some cases, enhanced antibacterial activity can be attributed to surface defects on ZnO abrasive surface texture. One functional application of the ZnO antibacterial bioactivity was discussed in food packaging industry where ZnO-NPs are used as an antibacterial agent toward foodborne diseases. Proper incorporation of ZnO-NPs into packaging materials can cause interaction with foodborne pathogens, thereby releasing NPs onto food surface where they come in contact with bad bacteria and cause the bacterial death and/or inhibition.

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Review on Zinc Oxide Nanoparticles: Antibacterial Activity and Toxicity Mechanism.

Antimicrobial nanomaterials for water disinfection and microbial control: Potential applications and implications

"Nanoantibiotics": a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era.

The antibacterial properties of zinc oxide nanoparticles were investigated using both Gram-positive and Gram-negative microorganisms. These studies demonstrate that ZnO nanoparticles have a wide range of antibacterial activities toward various microorganisms that are commonly found in environmental settings. The antibacterial activity of the ZnO nanoparticles was inversely proportional to the size of the nanoparticles in S. aureus. Surprisingly, the antibacterial activity did not require specific UV activation using artificial lamps, rather activation was achieved under ambient lighting conditions. Northern analyses of various reactive oxygen species (ROS) specific genes and confocal microscopy suggest that the antibacterial activity of ZnO nanoparticles might involve both the production of reactive oxygen species and the accumulation of nanoparticles in the cytoplasm or on the outer membranes. Overall, the experimental results suggest that ZnO nanoparticles could be developed as antibacterial agents agai...

Size-Dependent Bacterial Growth Inhibition and Mechanism of Antibacterial Activity of Zinc Oxide Nanoparticles

The antibacterial effect of zinc oxide (ZnO) nanoparticles on Campylobacter jejuni was investigated for inhibition and inactivation of cell growth. The results showed that C. jejuni was extremely sensitive to treatment with ZnO nanoparticles. The MIC of ZnO nanoparticles for C. jejuni was determined to be 0.05 to 0.025 mg/ml, which is 8- to 16-fold lower than that for Salmonella enterica serovar Enteritidis and Escherichia coli O157:H7 (0.4 mg/ml). The action of ZnO nanoparticles against C. jejuni was determined to be bactericidal, not bacteriostatic. Scanning electron microscopy examination revealed that the majority of the cells transformed from spiral shapes into coccoid forms after exposure to 0.5 mg/ml of ZnO nanoparticles for 16 h, which is consistent with the morphological changes of C. jejuni under other stress conditions. These coccoid cells were found by ethidium monoazide-quantitative PCR (EMA-qPCR) to have a certain level of membrane leakage. To address the molecular basis of ZnO nanoparticle action, a large set of genes involved in cell stress response, motility, pathogenesis, and toxin production were selected for a gene expression study. Reverse transcription-quantitative PCR (RT-qPCR) showed that in response to treatment with ZnO nanoparticles, the expression levels of two oxidative stress genes (katA and ahpC) and a general stress response gene (dnaK) were increased 52-, 7-, and 17-fold, respectively. These results suggest that the antibacterial mechanism of ZnO nanoparticles is most likely due to disruption of the cell membrane and oxidative stress in Campylobacter.

Antibacterial Activity and Mechanism of Action of Zinc Oxide Nanoparticles against Campylobacter jejuni

We report on the toxicity of ZnO nanoparticles (NPs) to gram-negative and gram-positive bacterial systems, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and primary human immune cells. ZnO NP (~13 nm) showed complete inhibition of E. coli growth at concentrations 3.4 mM, whereas growth of S. aureus was completely inhibited for 1 mM. Parallel experiments using flow cytometry based assays clearly demonstrated that growth inhibitory properties of ZnO NP were accompanied by a corresponding loss of cell viability. Identical ZnO NP had minimal effects on primary human T cell viability at concentrations toxic to both gram-negative and gram-positive bacteria. Collectively, these experiments demonstrate selectivity in the toxic nature of ZnO NP to different bacterial systems and human T lymphocytes. Developing selective toxicity to biological systems and controlling it by NP design could lead to biomedical and antibacterial applications.

Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems

Nanotechnology represents a new and enabling platform that promises to provide a range of innovative technologies for biological applications. ZnO nanoparticles of controlled size were synthesized, and their cytotoxicity toward different human immune cells evaluated. A differential cytotoxic response between human immune cell subsets was observed, with lymphocytes being the most resistant and monocytes being the most susceptible to ZnO nanoparticle-induced toxicity. Significant differences were also observed between previously activated memory lymphocytes and naive lymphocytes, indicating a relationship between cell-cycle potential and nanoparticle susceptibility. Mechanisms of toxicity involve the generation of reactive oxygen species, with monocytes displaying the highest levels, and the degree of cytotoxicity dependent on the extent of nanoparticle interactions with cellular membranes. An inverse relationship between nanoparticle size and cytotoxicity, as well as nanoparticle size and reactive oxygen species production was observed. In addition, ZnO nanoparticles induce the production of the proinflammatory cytokines, IFN-γ, TNF-α, and IL-12, at concentrations below those causing appreciable cell death. Collectively, these results underscore the need for careful evaluation of ZnO nanoparticle effects across a spectrum of relevant cell types when considering their use for potential new nanotechnology-based biological applications.

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The Influences of Cell Type and ZnO Nanoparticle Size on Immune Cell Cytotoxicity and Cytokine Induction

Fluorescein isothiocyanate (FITC)-encapsulated SiO(2) core-shell particles with a nanoscale ZnO finishing layer have been synthesized for the first time as multifunctional "smart" nanostructures. Detailed characterization studies confirmed the formation of an outer ZnO layer on the SiO(2)-FITC core. These approximately 200 nm sized particles showed promise toward cell imaging and cellular uptake studies using the bacterium Escherichia coli and Jurkat cancer cells, respectively. The FITC encapsulated ZnO particles demonstrated excellent selectivity in preferentially killing Jurkat cancer cells with minimal toxicity to normal primary immune cells (18% and 75% viability remaining, respectively, after exposure to 60 microg/ml) and inhibited the growth of both gram-positive and gram-negative bacteria at concentrations > or =250-500 microg/ml (for Staphylococcus aureus and Escherichia coli, respectively). These results indicate that the novel FITC encapsulated multifunctional particles with nanoscale ZnO surface layer can be used as smart nanostructures for particle tracking, cell imaging, antibacterial treatments and cancer therapy.

Fluorescent Dye Encapsulated ZnO Particles with Cell-Specific Toxicity for Potential Use in Biomedical Applications

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Cory Hanley

Papers

Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems

The Influences of Cell Type and ZnO Nanoparticle Size on Immune Cell Cytotoxicity and Cytokine Induction

Fluorescent Dye Encapsulated ZnO Particles with Cell-Specific Toxicity for Potential Use in Biomedical Applications

Differential Cellular Responses to Metal Oxide Based Nanoparticles and Potential Biomedical Applications