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      Metal-Based Nanoparticles as Antimicrobial Agents: An Overview

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          Abstract

          Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.

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          Review on Zinc Oxide Nanoparticles: Antibacterial Activity and Toxicity Mechanism

          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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            Metal nanoparticles: understanding the mechanisms behind antibacterial activity

            As the field of nanomedicine emerges, there is a lag in research surrounding the topic of nanoparticle (NP) toxicity, particularly concerned with mechanisms of action. The continuous emergence of bacterial resistance has challenged the research community to develop novel antibiotic agents. Metal NPs are among the most promising of these because show strong antibacterial activity. This review summarizes and discusses proposed mechanisms of antibacterial action of different metal NPs. These mechanisms of bacterial killing include the production of reactive oxygen species, cation release, biomolecule damages, ATP depletion, and membrane interaction. Finally, a comprehensive analysis of the effects of NPs on the regulation of genes and proteins (transcriptomic and proteomic) profiles is discussed.
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              Mechanisms of Antibiotic Resistance.

              Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic "attack" is the prime example of bacterial adaptation and the pinnacle of evolution. "Survival of the fittest" is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.
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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                09 February 2020
                February 2020
                : 10
                : 2
                : 292
                Affiliations
                [1 ]Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain; gerard.esteruelas.n@ 123456gmail.com (G.E.); bonilla.vidal95@ 123456gmail.com (L.B.); lora_ana@ 123456hotmail.com (A.L.L.-M.); ruth.galindo@ 123456ub.edu (R.G.); amanda90cf@ 123456gmail.com (A.C.); m.espina@ 123456ub.edu (M.E.); marisagarcia@ 123456ub.edu (M.L.G.)
                [2 ]Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain
                [3 ]Networking Research Centre of Neurodegenerative Disease (CIBERNED), Instituto de Salud Juan Carlos III, 28031 Madrid, Spain; e_miren60@ 123456hotmail.com (M.E.); camins@ 123456ub.edu (A.C.)
                [4 ]Faculty of Pharmacy (FFUC), Department of Pharmaceutical Technology, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; dlsgomes@ 123456live.com.pt
                [5 ]Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
                [6 ]Department of Biology and Environment, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, P-5001-801 Vila Real, Portugal; amsilva@ 123456utad.pt
                [7 ]Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Quinta de Prados, P-5001-801 Vila Real, Portugal
                [8 ]CREA—Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Rome, Italy; alessandra.durazzo@ 123456crea.gov.it
                [9 ]Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy; asantini@ 123456unina.it
                [10 ]CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
                Author notes
                Author information
                https://orcid.org/0000-0003-2571-108X
                https://orcid.org/0000-0001-9567-4283
                https://orcid.org/0000-0003-1269-3847
                https://orcid.org/0000-0002-1229-5956
                https://orcid.org/0000-0002-7524-9914
                https://orcid.org/0000-0002-7747-9107
                https://orcid.org/0000-0001-5505-3327
                https://orcid.org/0000-0002-9737-6017
                Article
                nanomaterials-10-00292
                10.3390/nano10020292
                7075170
                32050443
                f2e40499-a3b4-4b01-8383-3dc415a24fde
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 November 2019
                : 29 January 2020
                Categories
                Review

                antibacterial activity,metal-based nanoparticles,agnps,cuonps,aunps,znonps

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