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

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Abstract 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
The mechanisms of action of current anti‐infective agents, including potential resistance mechanisms against (a) antibiotics and (b) antivirals
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The number of publications (a) on nanomedicines and (b) investigating the potential applications of MONPs as antimicrobial agents published per year from 2004 to 2018 (data extracted from PubMed using the search term “nanomedicines” and “metal oxide nanoparticles as antimicrobial agents” on June 13, 2019)
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A schematic showing the major immune responses against an invading pathogen
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Challenges potentially facing NPs after oral, topical, and IV administration. NPs, nanoparticles
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Mechanisms of action of metal oxide nanoparticles as antiviral agents
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Mechanisms of action involved when metal oxide nanoparticles act as antibacterial agents
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Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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