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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Metal-based nanoparticles as antimicrobial agents: an overview.

Since discovery of the first antibiotic drug, penicillin, in 1928, a variety of antibiotic and antimicrobial agents have been developed and used for both human therapy and industrial applications. However, excess and uncontrolled use of antibiotic agents has caused a significant growth in the number of drug resistant pathogens. Novel therapeutic approaches replacing the inefficient antibiotics are in high demand to overcome increasing microbial multidrug resistance. In the recent years, ongoing research has focused on development of nano-scale objects as efficient antimicrobial therapies. Among the various nanoparticles, silver nanoparticles have gained much attention due to their unique antimicrobial properties. However, concerns about the synthesis of these materials such as use of precursor chemicals and toxic solvents, and generation of toxic byproducts have led to a new alternative approach, green synthesis. This eco-friendly technique incorporates use of biological agents, plants or microbial agents as reducing and capping agents. Silver nanoparticles synthesized by green chemistry offer a novel and potential alternative to chemically synthesized nanoparticles. In this review, we discuss the recent advances in green synthesis of silver nanoparticles, their application as antimicrobial agents and mechanism of antimicrobial mode of action.

https://pubs.rsc.org/en/content/articlepdf/2019/ra/c8ra08982e

Green synthesis of silver nanoparticles: biomolecule-nanoparticle organizations targeting antimicrobial activity

Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies. Bacteria have developed many ways by which they become resistant to antimicrobials. Among those are enzyme inactivation, decreased cell permeability, target protection, target overproduction, altered target site/enzyme, increased efflux due to over-expression of efflux pumps, among others. Other more complex phenotypes, such as biofilm formation and quorum sensing do not appear as a result of the exposure of bacteria to antibiotics although, it is known that biofilm formation can be induced by antibiotics. These phenotypes are related to tolerance to antibiotics in bacteria. Different strategies, such as the use of nanostructured materials, are being developed to overcome these and other types of resistance. Nanostructured materials can be used to convey antimicrobials, to assist in the delivery of novel drugs or ultimately, possess antimicrobial activity by themselves. Additionally, nanoparticles (e.g., metallic, organic, carbon nanotubes, etc.) may circumvent drug resistance mechanisms in bacteria and, associated with their antimicrobial potential, inhibit biofilm formation or other important processes. Other strategies, including the combined use of plant-based antimicrobials and nanoparticles to overcome toxicity issues, are also being investigated. Coupling nanoparticles and natural-based antimicrobials (or other repurposed compounds) to inhibit the activity of bacterial efflux pumps; formation of biofilms; interference of quorum sensing; and possibly plasmid curing, are just some of the strategies to combat multidrug resistant bacteria. However, the use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome this. In this review, we will summarize the current research on nanoparticles and other nanomaterials and how these are or can be applied in the future to fight multidrug resistant bacteria.

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Nano-Strategies to Fight Multidrug Resistant Bacteria-"A Battle of the Titans".

Silver nanoparticles (AgNPs) can be synthesized from a variety of techniques including physical, chemical and biological routes. They have been widely used as nanomaterials for manufacturing cosmetic and healthcare products, antimicrobial textiles, wound dressings, antitumor drug carriers, etc. due to their excellent antimicrobial properties. Accordingly, AgNPs have gained access into our daily life, and the inevitable human exposure to these nanoparticles has raised concerns about their potential hazards to the environment, health, and safety in recent years. From in vitro cell cultivation tests, AgNPs have been reported to be toxic to several human cell lines including human bronchial epithelial cells, human umbilical vein endothelial cells, red blood cells, human peripheral blood mononuclear cells, immortal human keratinocytes, liver cells, etc. AgNPs induce a dose-, size- and time-dependent cytotoxicity, particularly for those with sizes ≤10 nm. Furthermore, AgNPs can cross the brain blood barrier of mice through the circulation system on the basis of in vivo animal tests. AgNPs tend to accumulate in mice organs such as liver, spleen, kidney and brain following intravenous, intraperitoneal, and intratracheal routes of administration. In this respect, AgNPs are considered a double-edged sword that can eliminate microorganisms but induce cytotoxicity in mammalian cells. This article provides a state-of-the-art review on the synthesis of AgNPs, and their applications in antimicrobial textile fabrics, food packaging films, and wound dressings. Particular attention is paid to the bactericidal activity and cytotoxic effect in mammalian cells.

Bactericidal and Cytotoxic Properties of Silver Nanoparticles.

The green synthesis of nanoparticles (NPs) using living cells is a promising and novelty tool in bionanotechnology. Chemical and physical methods are used to synthesize NPs; however, biological methods are preferred due to its eco-friendly, clean, safe, cost-effective, easy, and effective sources for high productivity and purity. High pressure or temperature is not required for the green synthesis of NPs, and the use of toxic and hazardous substances and the addition of external reducing, stabilizing, or capping agents are avoided. Intra- or extracellular biosynthesis of NPs can be achieved by numerous biological entities including bacteria, fungi, yeast, algae, actinomycetes, and plant extracts. Recently, numerous methods are used to increase the productivity of nanoparticles with variable size, shape, and stability. The different mechanical, optical, magnetic, and chemical properties of NPs have been related to their shape, size, surface charge, and surface area. Detection and characterization of biosynthesized NPs are conducted using different techniques such as UV-vis spectroscopy, FT-IR, TEM, SEM, AFM, DLS, XRD, zeta potential analyses, etc. NPs synthesized by the green approach can be incorporated into different biotechnological fields as antimicrobial, antitumor, and antioxidant agents; as a control for phytopathogens; and as bioremediative factors, and they are also used in the food and textile industries, in smart agriculture, and in wastewater treatment. This review will address biological entities that can be used for the green synthesis of NPs and their prospects for biotechnological applications.

Green Synthesis of Metallic Nanoparticles and Their Prospective Biotechnological Applications: an Overview

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.

https://link.springer.com/content/pdf/10.1186/s12951-017-0308-z.pdf

Metal nanoparticles: understanding the mechanisms behind antibacterial activity.

Molds are filamentous fungi able to grow on a variety of surfaces, including constructed surfaces, food, rotten organic matter, and humid places. Mold growth is characterized by having an unpleasant odor in enclosed or non-ventilated places and a non-aesthetic appearance. They represent a health concern because of their ability to produce and release mycotoxins, compounds that are toxic to animals and humans. The aim of this study was to evaluate commercial nanoparticles (NPs) that can be used as an additive in coatings and paints to effectively control the growth of harmful molds. Four different NPs were screened for their antifungal activities against the mycotoxin producing mold strains Aspergillus flavus and A. fumigatus. The minimal inhibitory concentrations of the NPs were determined in broth media, whereas an agar diffusion test was used to assess the antimold activity on acrylic- and water-based paints. The cytotoxic activity and the inflammatory response of the NPs were also evaluated using the established human derived macrophage cell line THP-1. Results showed that a combination of mix metallic- and ZnO-NPs (50:10 μg/mL) effectively inhibited the fungal growth when exposed to fluorescent light. Neither cytotoxic effect nor inflammatory responses were recorded, suggesting that this combination can be safely used in humid or non-ventilated environments without any health concerns.

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Jason Asnis

Papers

Metal nanoparticles: understanding the mechanisms behind antibacterial activity.

Effective Control of Molds Using a Combination of Nanoparticles

Rapid microwave-based method for the preparation of antimicrobial lignin-capped silver nanoparticles active against multidrug-resistant bacteria.