The potential anti‐infective applications of metal oxide nanoparticles: A systematic review

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Abstract

<p class="first" id="d2814247e69">Microbial infections present a major global healthcare challenge, in large part because of the development of microbial resistance to the currently approved antimicrobial drugs. This demands the development of new antimicrobial agents. Metal oxide nanoparticles (MONPs) are a class of materials that have been widely explored for diagnostic and therapeutic purposes. They are reported to have wide-ranging antimicrobial activities and to be potent against bacteria, viruses, and protozoans. The use of MONPs reduces the possibility of resistance developing because they have multiple mechanisms of action (including via reactive oxygen species generation), simultaneously attacking many sites in the microorganism. However, despite this there are to date no MONPs clinically approved for antimicrobial therapy. This review explores the recent literature in this area, discusses the mechanisms of MONP action against microorganisms, and considers the barriers faced to the use of MONPs in humans. These include biological challenges, of which the potential for an immune response and off-target toxicity are key. We explore in detail the possible benefits/disbenefits of an immune response being initiated, and consider the effect of production method (chemical vs. green synthesis) on cytotoxicity. There are also a number of technical and manufacturing challenges hindering MONP translation to the clinic which are additionally discussed in depth. In the short term, there are potentially some "quick wins" from the repurposing of already-approved nanoparticle-based medicines for anti-infective applications, but a number of hurdles, both technical and biological, lie in the path to long-term clinical translation of new MONP-based formulations. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials. </p>

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Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the Gram-negative bacterium Escherichia coli.

Sukdeb Pal, Yu Tak, Joon Myong Song (2007)

In this work we investigated the antibacterial properties of differently shaped silver nanoparticles against the gram-negative bacterium Escherichia coli, both in liquid systems and on agar plates. Energy-filtering transmission electron microscopy images revealed considerable changes in the cell membranes upon treatment, resulting in cell death. Truncated triangular silver nanoplates with a {111} lattice plane as the basal plane displayed the strongest biocidal action, compared with spherical and rod-shaped nanoparticles and with Ag(+) (in the form of AgNO(3)). It is proposed that nanoscale size and the presence of a {111} plane combine to promote this biocidal property. To our knowledge, this is the first comparative study on the bactericidal properties of silver nanoparticles of different shapes, and our results demonstrate that silver nanoparticles undergo a shape-dependent interaction with the gram-negative organism E. coli.

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Doxil®--the first FDA-approved nano-drug: lessons learned.

Yechezkel Barenholz (2012)

Doxil®, the first FDA-approved nano-drug (1995), is based on three unrelated principles: (i) prolonged drug circulation time and avoidance of the RES due to the use of PEGylated nano-liposomes; (ii) high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in a "liquid ordered" phase composed of the high-T(m) (53 °C) phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is "passively targeted" to tumors and its doxorubicin is released and becomes available to tumor cells by as yet unknown means. This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use. It demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles. However, in spite of the large reward, ~2 years after Doxil-related patents expired, there is still no FDA-approved generic "Doxil" available. Copyright © 2012 Elsevier B.V. All rights reserved.

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Antibiotics and Bacterial Resistance in the 21st Century

Richard Fair, Yitzhak Tor (2014)

Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. Synchronously with the waxing of bacterial resistance there has been waning antibiotic development. The approaches that scientists are employing in the pursuit of new antibacterial agents are briefly described. The standings of established antibiotic classes as well as potentially emerging classes are assessed with an emphasis on molecules that have been clinically approved or are in advanced stages of development. Historical perspectives, mechanisms of action and resistance, spectrum of activity, and preeminent members of each class are discussed.